Association between maternal employment status and presence of children with major congenital anomalies in Denmark.

IMPORTANCE: The burden of caring for children with complex medical problems such as major congenital anomalies falls principally on mothers, who in turn suffer a variety of potentially severe economic consequences. As well, health consequences of caregiving often further impact the social and economic prospects of mothers of children with major congenital anomalies (MCMCAs). Evaluating the long-term economic consequences of extensive in-home caregiving among MCMCAs can inform strategies to mitigate these effects. OBJECTIVE: To assess whether MCMCAs face reduced employment and increased need for disability benefits over a 20-year period. DESIGN: A population-based matched cohort study. SETTING: Denmark. PARTICIPANTS: All women who gave birth to a singleton child with a major congenital anomaly in Denmark between January 1, 1997 and December 31, 2017 (n = 23,637) and a comparison cohort of mothers matched by maternal age, parity, and infant's year of birth (n = 234,586). EXPOSURES: Liveborn infant with a major congenital anomaly. MAIN OUTCOMES AND MEASURES: The primary outcome was mothers' employment status, stratified by their child's age. Employment status was categorized as employed, outside the workforce (on temporary leave, holding a flexible job, or pursuing education), or unemployed; the number of weeks in each category was measured over time. The secondary outcome was time to receipt of a disability pension, which in Denmark implies permanent exit from the labor market. We used a negative binomial regression model to estimate the number of weeks in each employment category, stratified by the child's age (i.e., 0-1 year, > 1-6 years, 7-13 years, 14-18 years). A Cox proportional hazards regression model was used to compute hazard ratios as a measure of the relative risk of receiving a disability pension. Rate ratios and hazard ratios were adjusted for maternal demographics, pregnancy history, health, and infant's year of birth. RESULTS: During 1-6 years after delivery, MCMCAs were outside the workforce for a median of 50 weeks (IQR, 6-107 weeks), while members of the comparison cohort were outside the workforce for a median of 48 weeks (IQR, 4-98 weeks), corresponding to an adjusted rate ratio [ARR] of 1.05 (95% confidence interval [CI], 1.04-1.07). During the first year after delivery, MCMCAs were more likely to be employed than mothers in the comparison cohort (ARR, 1.08; 95% CI, 1.06-1.10). At all timepoints thereafter, MCMCAs had a lower rate of workforce participation. The rate of being outside the workforce was 5% higher than mothers in the comparison cohort during 1-6 years after delivery (ARR, 1.05; 95% CI, 1.04-1.07), 9% higher during 7-13 years after delivery (ARR, 1.09; 95% CI, 1.06-1.12), and 12% higher during 14-18 years after delivery (ARR, 1.12; 95% CI, 1.07-1.18). Overall, MCMCAs had a 20% increased risk of receiving a disability pension during follow-up than mothers in the matched comparison cohort [incidence rates 3.10 per 1000 person-years (95% CI, 2.89-3.32) vs. 2.34 per 1000 person-years (95% CI, 2.29-2.40), adjusted hazard ratio, 1.20; 95% CI, 1.11-1.29]. CONCLUSION AND RELEVANCE: MCMCAs were less likely to participate in the Danish workforce, less likely to be employed, and more likely to receive disability pensions than mothers of unaffected children. The rate of leaving the workforce intensified as their affected children grew older. The high demands of caregiving among MCMCAs may have long-term employment consequences even in nations with comprehensive and heavily tax-supported childcare systems, such as Denmark.

Comparison of Estimated Incentives for Preventing Postpartum Depression in Value-Based Payment Models Using the Net Present Value of Care vs Total Cost of Care.

Importance: Strong financial incentives are critical to promoting widespread implementation of interventions that prevent postpartum depression. Value-based payment (VBP) approaches could be adapted to capture longer-term value and offer stronger incentives for postpartum depression prevention by sharing the expected future health care savings estimated by reduced postpartum depression incidence with clinicians. Objective: To evaluate whether sharing 5-year expected savings estimated by reduced postpartum depression incidence offers stronger incentives for prevention than traditional VBP under a variety of circumstances. Design, Setting, and Participants: This decision analytic model used a simulated cohort of 1000 Medicaid-enrolled pregnant individuals. Health care costs for individuals receiving postpartum depression preventive intervention or not, over 1 or 5 years post partum, in a variety of scenarios, including varying rates of Medicaid churn (ie, transitions to a new Medicaid managed care plan, commercial insurance plan, or loss of coverage) were estimated for the period 2020 to 2025. The model was developed between March 5 and July 30, 2021. Exposure: Sharing 100% of 1-year actual health care cost saving vs 50% of 5-year estimated health care cost savings associated with reduced postpartum depression incidence. Main Outcomes and Measures: The main outcome was the amount of clinician incentive shared in a VBP model from providing preventive interventions. The likelihood of the health care payer realizing a positive return on investment if it shared 50% of 5-year expected savings with a clinician up front was also measured. Results: The simulated cohort was designed to be reflective of the demographics characteristics of pregnant individuals receiving Medicaid; however, no specific demographic features were simulated. Providing preventive interventions for postpartum depression resulted in an estimated 5-year savings of $734.12 (95% credible interval [CrI], $217.21-$1235.67) per person. Without health insurance churn, sharing 50% of 5-year expected savings could offer more than double the financial incentives for clinicians to prevent postpartum depression compared with traditional VBP ($367.06 [95% CrI, $108.61-$617.83] vs $177.74 [95% CrI, $52.66-$296.60], respectively), with a high likelihood of positive return for the health care payer (91%). As health insurance churn increased, clinician incentives from sharing estimated savings decreased (73% reduction with 50% annual churn). Conclusions and Relevance: In this decision analytic model of VBP approaches to incentivizing postpartum depression prevention, VBP based on 5-year expected savings offered stronger incentives when churn was low. Policy should support health care payers and clinicians to share estimated savings and overcome health insurance churn issues to promote wide-scale implementation of interventions to prevent perinatal mental health conditions.

Distilling innovative US autism care programs that address widely perceived unmet patient and family needs.

LAY ABSTRACT: Currently, the quality of care for autistic individuals is not good. Many care services for autistic individuals are not well coordinated, nor are they tailored. We wanted to find out a better model for autism care and believed that the autism community knows where these programs are. So, we had conversations with and surveyed 55 autistic adults, family members, clinicians, and researchers. They shared 90 innovative autism care programs that had been collaboratively designed with patients and families and that are likely to improve the quality of life of autistic individuals and their families. We then narrowed down the 90 nominated programs to 15 programs across the United States by applying researcher-selected criteria, such as providing services actively and having data on program effectiveness. We compiled a list of these innovative, quality autism care programs.

Mothers of children with major congenital anomalies have increased health care utilization over a 20-year post-birth time horizon.

OBJECTIVE: This population-based, matched cohort study aimed to evaluate utilization of health care services by mothers of children with major congenital anomalies (MCAs), compared to mothers of children without MCAs over a 20-year post-birth time horizon in Denmark. METHODS: Our analytic sample included mothers who gave birth to an infant with a MCA (n = 23,927) and a cohort of mothers matched to them by maternal age, parity and infant's year of birth (n = 239,076). Primary outcomes were period prevalence and mothers' quantity of health care utilization (primary, inpatient, outpatient, surgical, and psychiatric services) stratified by their child's age (i.e., ages 0-6 = before school, ages 7-13 = pre-school + primary education, and ages 14-18 = secondary education or higher). The secondary outcome measure was length of hospital stays. Outcome measures were adjusted for maternal age at delivery, parity, marital status, income quartile, level of education in the year prior to the index birth, previous spontaneous abortions, maternal pregnancy complications, maternal diabetes, hypertension, alcohol-related diseases, and maternal smoking. RESULTS: In both cohorts the majority of mothers were between 26 and 35 years of age, married, and employed, and 47% were primiparous. Mothers of infants with anomalies had greater utilization of outpatient, inpatient, surgical, and psychiatric services, compared with mothers in the matched cohort. Inpatient service utilization was greater in the exposed cohort up to 13 years after a child's birth, with the highest risk in the first six years after birth [adjusted risk ratio, 1.13; 95% confidence interval (CI), 1.12-1.14], with a decrease over time. Regarding the quantity of health care utilization, the greatest difference between the two groups was in inpatient service utilization, with a 39% increased rate in the exposed cohort during the first six years after birth (adjusted rate ratio, 1.39; 95% CI, 1.37-1.42). During the first 6 years after birth, mothers of children with anomalies stayed a median of 6 days (interquartile range [IQR], 3-13) in hospital overall, while the comparison cohort stayed a median of 4 days (IQR, 2-7) in hospital overall. Rates of utilization of outpatient clinics (adjusted rate ratio, 1.36; 95% CI, 1.29-1.42), as well as inpatient (adjusted rate ratio, 1.77; 95% CI, 1.68-1.87), and surgical services (adjusted rate ratio, 1.33; 95% CI, 1.26-1.41) was higher in mothers of children with multiple-organ MCAs during 0 to 6 years after birth. Among mothers at the lowest income levels, utilization of psychiatric clinic services increased to 59% and when their child was 7 to 13 years of age (adjusted rate ratio, 1.59; 95% CI, 1.24-2.03). CONCLUSION: Mothers of infants with a major congenital anomaly had greater health care utilization across services. Health care utilization decreased over time or remained stable for outpatient, inpatient, and surgical care services, whereas psychiatric utilization increased for up to 13 years after an affected child's birth. Healthcare utilization was significantly elevated among mothers of children with multiple MCAs and among those at the lowest income levels.

Psychometric properties of the Chinese version of Five Facet Mindfulness Questionnaire-short form in cancer patients: a Bayesian structural equation modeling approach.

BACKGROUND: Mindfulness has emerged as an important correlate of well-being in various clinical populations. The present study evaluated the psychometric properties of the 20-item short form of the Five Facet Mindfulness Questionnaire (FFMQ-SF) in the Chinese context. METHODS: The study sample was 127 Chinese colorectal cancer patients who completed the FFMQ-SF and validated physical and mental health measures. Factorial validity of the FFMQ-SF was assessed using Bayesian structural equation modeling (BSEM) via informative priors on cross-loadings and residual covariances. Linear regression analysis examined its convergent validity with the health measures on imputed datasets. RESULTS: The five-factor BSEM model with approximate zero cross-loadings and one residual covariance provided an adequate model fit (PPP = 0.07, RMSEA = 0.06, CFI = 0.95). Satisfactory reliability (ω = 0.77-0.85) was found in four of the five facets (except nonjudging). Acting with awareness predicted lower levels of perceived stress, negative affect, anxiety, depression, and illness symptoms (ß = - 0.37 to - 0.42) and better quality of life (ß = 0.29-0.32). Observing, nonjudging, and nonreacting did not show any significant associations (p > .05) with health measures. Acting with awareness was not significantly correlated (r < 0.15) with the other four facets. CONCLUSION: The present findings provide partial support for the psychometric properties of the FFMQ-SF in colorectal cancer patients. The nonjudging facet showed questionable validity and reliability in the present sample. Further studies with larger sample sizes are needed to elucidate the viability of FFMQ-SF as a measure of mindfulness facets in cancer patients.

Achieving better value in pediatric care: school systems as clinical and financial partners?

This article argues that value-based health systems may contract with school districts engaged in capitated special education to achieve better patient outcomes and lower costs for the pediatric population.

Implementation Fidelity and Common Elements of High Quality Teaching Sequences for Students with Autism Spectrum Disorder in COMPASS.

BACKGROUND: Evidence-based educational instruction includes teaching elements common across different approaches as well as specific elements of the chosen evidence-based practice. We were interested in evaluating the use and impact of common elements of teaching. Specifically, we adopted a model of elements of high quality teaching sequences and developed and tested an instructional quality index to capture evidence-based features within teaching sequences (Grisham-Brown & Ruble, 2014). METHOD: The current investigation examined 29 special education teachers who received a consultation intervention called the Collaborative Model for Promoting Competence and Success (COMPASS; Ruble, Dalrymple & McGrew, 2012) that results in personalized teaching plans for young students with ASD and embeds elements of evidence-based teacher coaching of self-reflection and performance-based feedback. We analyzed the teaching plans to understand which of the common elements were present, and if teachers demonstrated improved performance after coaching. RESULTS: Analysis of the use of common elements during the first and fourth coaching session demonstrated that all teachers showed improvement. Most importantly, the use of common elements correlated with student goal attainment outcomes. CONCLUSIONS: These results suggest that common elements of teaching sequences which we view as core features of teaching quality, can be improved as a result of coaching, and most importantly, are associated with students' educational outcomes.

Predicting the Outcomes of Parents of Transition-Age Youth or Young Adults with ASD.

The transition outcomes for individuals with autism spectrum disorder (ASD) and their families are less than desirable. A survey of parent stressors, resources, coping/appraisals, and adaptation to transition was completed by 226 parents. The mediating mechanisms between stressors and parent outcomes were identified. At the indicator level, three stressors (i.e., autism severity, mental health crisis/challenging behaviors, and filial obligation), four resources (i.e., general social support, transition planning quality, parent-teacher alliance, and parenting efficacy), and three coping styles (i.e., problem-focused coping, avoidance-focused coping, and optimism) predicted parents' outcomes (i.e., burden, transition experience, subjective health, and quality of life). At the structural level, optimism, emotion-coping strategies, and resources mediated the relationships between stressors and parental outcomes. Research and practical applications are discussed.

A Preliminary Study of Parent Activation, Parent-Teacher Alliance, Transition Planning Quality, and IEP and Postsecondary Goal Attainment of Students with ASD.

The school, student and family factors underlying poor postsecondary outcomes of students with autism spectrum disorder (ASD) are not well understood. The potential impact of school [e.g., transition planning quality (TPQ)], family (e.g., parent activation), and student factors (e.g., adaptive functioning) and their interaction (e.g., parent-teacher alliance) on student outcomes were examined. Student IQ and adaptive behavior, TPQ, and alliance correlated with IEP progress, with postsecondary goal attainment generally and with student participation in training/education, specifically. However, only parent activation and student externalizing behavior correlated with employment. Families and students, rather than school personnel, were the primary persons in charge and in control of the implementation of postsecondary plans and required help across multiple coaching sessions to implement plans fully.

An empirical study of multidimensional fidelity of COMPASS consultation.

Consultation is essential to the daily practice of school psychologists (National Association of School Psychologist, 2010). Successful consultation requires fidelity at both the consultant (implementation) and consultee (intervention) levels. We applied a multidimensional, multilevel conception of fidelity (Dunst, Trivette, & Raab, 2013) to a consultative intervention called the Collaborative Model for Promoting Competence and Success (COMPASS) for students with autism. The study provided 3 main findings. First, multidimensional, multilevel fidelity is a stable construct and increases over time with consultation support. Second, mediation analyses revealed that implementation-level fidelity components had distant, indirect effects on student Individualized Education Program (IEP) outcomes. Third, 3 fidelity components correlated with IEP outcomes: teacher coaching responsiveness at the implementation level, and teacher quality of delivery and student responsiveness at the intervention levels. Implications and future directions are discussed. (PsycINFO Database Record

Too Stressed to Teach? Teaching Quality, Student Engagement, and IEP Outcomes.

Teacher stress and burnout have a detrimental effect on the stability of the teaching workforce. However, the possible consequences of teacher burnout on teaching quality and on student learning outcomes are less clear, especially in special education settings. We applied Maslach and Leiter's model (1999) to understand the direct effects of burnout on teaching in general and stress arising from interaction with a specific student on the IEP outcomes of young children with autism spectrum disorder. We also examined indirect effects through teaching quality and student engagement. The results indicated that one of the three components of burnout-teacher personal accomplishment-was directly related to IEP outcomes, a distal effect, whereas stress was directly related to teaching quality and student engagement, which were more proximal effects. Additionally, teacher stress, emotional exhaustion, and depersonalization had indirect effects on IEP outcomes through teaching quality and student engagement.

Addressing holistic health and work empowerment through a body-mind-spirit intervention program among helping professionals in continuous education: A pilot study.

To examine the effectiveness of a body-mind-spirit (BMS) intervention program in improving the holistic well-being and work empowerment among helping professionals in continuous education. Forty-four helping professionals, who were in their first-year part-time postgraduate study, participated in the present study. All participants attended a 3-day BMS intervention program which emphasized a holistic approach to health and well-being. Ratings on their levels of physical distress, daily functioning, affect, spirituality, and psychological empowerment at work were compared before and immediately after the intervention. Participants reported significantly lower levels of negative affect and physical distress, and were less spiritually disoriented after the intervention. Enhanced levels of daily functioning, positive affect, spiritual resilience, and tranquility were also reported. Results also suggested that participants were empowered at work, and specifically felt more able to make an impact on work outcomes. The 3-day BMS intervention program produced a positive and measurable effect on participants' holistic well-being and empowerment at work. Educators in related fields could incorporate holistic practices into the curriculum to better prepare the future practitioners, leading to better outcomes both to the professionals themselves and their clients or patients.

Cultural model of self-stigma among Chinese with substance use problems.

BACKGROUND: Substance use is regarded as one of the most stigmatizing conditions worldwide. To achieve recovery, individuals with substance use problems must learn to cope with stigma. Despite the potential importance of cultural factors in the internalization process of stigma, few studies have incorporated culturally salient factors in understanding self-stigma. We responded to this gap in the literature by investigating a mechanism of self-stigma that focused on a cultural value salient to the Chinese-face concern. Specifically, we hypothesized that two types of face concern (mianzi concern and lian concern) would affect self-stigma and mental health through self-conscious moral emotions and rumination. METHODS: A total of 199 Hong Kong Chinese adults with substance use problems completed standardized questionnaires. RESULTS: Test of the proposed model using structural equation modeling showed excellent fit to the data. The findings support the role of face concern in affecting self-stigma and mental health among Chinese with substance use problems. In particular, the findings showed significant indirect effects of lian concern on rumination, self-stigma, and mental health via moral emotions. CONCLUSIONS: The present study provides preliminary empirical support for the importance of cultural factors in the internalization process of stigma and the maintenance of mental health among individuals with substance use problems.

Effectiveness of integrated body-mind-spirit group intervention on the well-being of Indian patients with depression: a pilot study.

BACKGROUND: Depression is a leading cause of disability worldwide. There is a need to develop effective strategies to treat depression and prevent recurrence. Treatments that combine pharmacological and psychotherapeutic approaches are preferred for treating severe forms of depression. PURPOSE: The study assesses the effect of an integrated body-mind-spirit group intervention in patients with depression. METHODS: This pilot study was a pretest-posttest design study. Thirty adult patients diagnosed with depression attending the psychiatric outpatient department at a district hospital were randomly assigned to either the intervention group or comparison group. Each group had 15 patients. The intervention group received both the intervention and routine hospital treatment and underwent four group integrated body-mind-spirit group intervention therapy sessions. These sessions were held once per week on either Saturday or Sunday, with each session lasting more than 3 hours. Comparison group participants received routine hospital treatment only. Outcome measures, including level of depression, well-being, and work and social adjustment, were measured using the Beck Depression Inventory-II, body-mind-spirit well-being scale, and work and social adjustment scale. Both groups were evaluated at baseline, 1 month, 2 months, and 3 months. RESULTS: Results showed that both groups had significant reductions in the level of depression, improvements in well-being, and work and social adjustment at 3-month follow-up compared with baseline. In addition, the intervention group showed significant mean differences in levels of depression, well-being, and work and social adjustment compared with the comparison group. CONCLUSION: The integrated body-mind-spirit group intervention model appears to reduce depressive symptoms and improve well-being in patients with depression.

The Fas/FasL pathway impairs the alveolar fluid clearance in mouse lungs.

Alveolar epithelial damage is a critical event that leads to protein-rich edema in acute lung injury (ALI), but the mechanisms leading to epithelial damage are not completely understood. Cell death by necrosis and apoptosis occurs in alveolar epithelial cells in the lungs of patients with ALI. Fas activation induces apoptosis of alveolar epithelial cells, but its role in the formation of lung edema is unclear. The main goal of this study was to determine whether activation of the Fas/Fas ligand pathway in the lungs could alter the function of the lung epithelium, and the mechanisms involved. The results show that Fas activation alters the alveolar barrier integrity and impairs the ability of the lung alveolar epithelium to reabsorb fluid from the air spaces. This result was dependent on the presence of a normal Fas receptor and was not affected by inflammation induced by Fas activation. Alteration of the fluid transport properties of the alveolar epithelium was partially restored by ß-adrenergic stimulation. Fas activation also caused apoptosis of alveolar endothelial cells, but this effect was less pronounced than the effect on the alveolar epithelium. Thus, activation of the Fas pathway impairs alveolar epithelial function in mouse lungs by mechanisms involving caspase-dependent apoptosis, suggesting that targeting apoptotic pathways could reduce the formation of lung edema in ALI.

Death receptors mediate the adverse effects of febrile-range hyperthermia on the outcome of lipopolysaccharide-induced lung injury.

We have shown that febrile-range hyperthermia enhances lung injury and mortality in mice exposed to inhaled LPS and is associated with increased TNF-α receptor activity, suppression of NF-κB activity in vitro, and increased apoptosis of alveolar epithelial cells in vivo. We hypothesized that hyperthermia enhances lung injury and mortality in vivo by a mechanism dependent on TNF receptor signaling. To test this, we exposed mice lacking the TNF-receptor family members TNFR1/R2 or Fas (TNFR1/R2(-/-) and lpr) to inhaled LPS with or without febrile-range hyperthermia. For comparison, we studied mice lacking IL-1 receptor activity (IL-1R(-/-)) to determine the role of inflammation on the effect of hyperthermia in vivo. TNFR1/R2(-/-) and lpr mice were protected from augmented alveolar permeability and mortality associated with hyperthermia, whereas IL-1R(-/-) mice were susceptible to augmented alveolar permeability but protected from mortality associated with hyperthermia. Hyperthermia decreased pulmonary concentrations of TNF-α and keratinocyte-derived chemokine after LPS in C57BL/6 mice and did not affect pulmonary inflammation but enhanced circulating markers of oxidative injury and nitric oxide metabolites. The data suggest that hyperthermia enhances lung injury by a mechanism that requires death receptor activity and is not directly associated with changes in inflammation mediated by hyperthermia. In addition, hyperthermia appears to enhance mortality by generating a systemic inflammatory response and not by a mechanism directly associated with respiratory failure. Finally, we observed that exposure to febrile-range hyperthermia converts a modest, survivable model of lung injury into a fatal syndrome associated with oxidative and nitrosative stress, similar to the systemic inflammatory response syndrome.

The biological activity of FasL in human and mouse lungs is determined by the structure of its stalk region.

Acute lung injury (ALI) is a life-threatening condition in critically ill patients. Injury to the alveolar epithelium is a critical event in ALI, and accumulating evidence suggests that it is linked to proapoptotic Fas/FasL signals. Active soluble FasL (sFasL) is detectable in the bronchoalveolar lavage (BAL) fluid of patients with ALI, but the mechanisms controlling its bioactivity are unclear. We therefore investigated how the structure of sFasL influences cellular activation in human and mouse lungs and the role of oxidants and proteases in modifying sFasL activity. The sFasL in BAL fluid from patients with ALI was bioactive and present in high molecular weight multimers and aggregates. Oxidants generated from neutrophil myeloperoxidase in BAL fluid promoted aggregation of sFasL in vitro and in vivo. Oxidation increased the biological activity of sFasL at low concentrations but degraded sFasL at high concentrations. The amino-terminal extracellular stalk region of human sFasL was required to induce lung injury in mice, and proteolytic cleavage of the stalk region by MMP-7 reduced the bioactivity of sFasL in human cells in vitro. The sFasL recovered from the lungs of patients with ALI contained both oxidized methionine residues and the stalk region. These data provide what we believe to be new insights into the structural determinants of sFasL bioactivity in the lungs of patients with ALI.

Febrile-range hyperthermia augments lipopolysaccharide-induced lung injury by a mechanism of enhanced alveolar epithelial apoptosis.

Fever is common in critically ill patients and is associated with worse clinical outcomes, including increased intensive care unit mortality. In animal models, febrile-range hyperthermia (FRH) worsens acute lung injury, but the mechanisms by which this occurs remain uncertain. We hypothesized that FRH augments the response of the alveolar epithelium to TNF-alpha receptor family signaling. We found that FRH augmented LPS-induced lung injury and increased LPS-induced mortality in mice. At 24 h, animals exposed to hyperthermia and LPS had significant increases in alveolar permeability without changes in inflammatory cells in bronchoalveolar lavage fluid or lung tissue as compared with animals exposed to LPS alone. The increase in alveolar permeability was associated with an increase in alveolar epithelial apoptosis and was attenuated by caspase inhibition with zVAD.fmk. At 48 h, the animals exposed to hyperthermia and LPS had an enhanced lung inflammatory response. In murine lung epithelial cell lines (MLE-15, LA-4) and in primary type II alveolar epithelial cells, FRH enhanced apoptosis in response to TNF-alpha but not Fas ligand. The increase in apoptosis was caspase-8 dependent and associated with suppression of NF-kappaB activity. The FRH-associated NF-kappaB suppression was not associated with persistence of IkappaB-alpha, suggesting that FRH-mediated suppression of NF-kappaB occurs by means other than alteration of IkappaB-alpha kinetics. These data show for the first time that FRH promotes lung injury in part by increasing lung epithelial apoptosis. The enhanced apoptotic response might relate to FRH-mediated suppression of NF-kappaB activity in the alveolar epithelium with a resultant increase in susceptibility to TNF-alpha-mediated cell death.