Food insecurity and mental health during the COVID-19 pandemic in cystic fibrosis households.

BACKGROUND: The COVID-19 pandemic impacted many households due to shelter-in-place orders and economic hardship. People with cystic fibrosis (CF) experienced increased food insecurity compared to the general population before the pandemic, even though adequate food access is needed to maintain nutrition goals associated with improved health-related outcomes. Little is known about the impact the pandemic had on the food insecurity of people with CF and their families. OBJECTIVE: To investigate how the COVID-19 pandemic impacted food insecurity, mental health, and self-care in people with CF. METHODS: Adults with CF and parents/guardians of children with CF were recruited via social media to complete online questionnaires from May 2020 to February 2021. Questionnaires in English and Spanish included USDA 2-question food insecurity screening, Patient Health Questionnaire-4 for mental health screening, and directed questions on the impact of the pandemic. RESULTS: Of 372 respondents, 21.8% of the households experienced food insecurity during the pandemic compared to 18.8% prepandemic (p < .001). More food insecure patients with CF reported weight loss (32.1% vs. 13.1%, p < .001), worse airway clearance adherence (13.6% vs. 5.8%, p < .01), and worse medication adherence (12.4% vs. 1.7%, p < .01) compared to food secure patients. Food insecure subjects were more likely to have an abnormal mental health screen compared to food secure subjects (53.1% vs. 16.2%, p < .001). CONCLUSION: Food insecurity increased in the CF population during the COVID-19 pandemic. Food insecure subjects reported worse mental health and self-care during the pandemic compared to food secure subjects.

Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children.

BACKGROUND: Despite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant mortality. Therefore, we aimed to develop a highly sensitive metagenomic next-generation sequencing (mNGS) assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children. METHODS: We collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at 3 children's hospitals from 2014-2016. Samples underwent mechanical homogenization, parallel RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the National Center for Biotechnology Information nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort. RESULTS: We identified a rich cross-domain pulmonary microbiome that contained bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median, 0.61; interquartile range [IQR], 0.33-0.72 vs median, 0.96; IQR, 0.94-0.96; P < .001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (P < .001). CONCLUSIONS: An optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease.

Sepsis and acute respiratory distress syndrome requiring extracorporeal life support in an adolescent with mild cystic fibrosis.

Outcomes for invasive mechanical ventilation and extracorporeal membrane oxygenation (ECMO) to treat acute respiratory failure in patients with mild cystic fibrosis (CF) lung disease are not known. We present a case of the successful use of ECMO to treat acute respiratory failure secondary to staphylococcal sepsis in an adolescent CF patient with previously normal lung function. Her post-ECMO course was notable for severe airflow obstruction, hypoxemia, deconditioning, and growth failure. She had significantly improved at six months follow-up, though she continued to have moderate airflow obstruction on pulmonary function testing. This case illustrates that ECMO and prolonged intubation can prolong life in CF patients with mild lung disease who present with potentially reversible acute respiratory failure, though they are associated with significant morbidity.

Long-Term Pulmonary Function and Quality of Life in Children After Acute Respiratory Distress Syndrome: A Feasibility Investigation.

OBJECTIVES: To determine the feasibility of pulmonary function and quality of life evaluations in children after acute respiratory distress syndrome. DESIGN: A prospective follow-up feasibility study. SETTING: A tertiary PICU. PATIENTS: Children less than 18 years old with acute respiratory distress syndrome admitted between 2000 and 2005. INTERVENTION: Pulmonary function testing and patient and parental quality of life surveys approximately 12-month after acute respiratory distress syndrome. MEASUREMENTS AND MAIN RESULTS: One hundred eighty patients met acute respiratory distress syndrome criteria; 37 (20%) died, 90 (51%) declined participation, 28 (16%) consented but did not return, and 24 (13%) returned for follow-up visit. Twenty-three patients completed quality of life testing and 17 completed pulmonary functions. Clinical characteristics of those who returned were no different from those who did not except for age (median age, 4.9 vs 1.8 yr). One-third had mild to moderate pulmonary function deficits. Quality of life scores were marginal with general health perception, physical functioning, and behavior being areas of concern. These scores were lower than scores in children with chronic asthma. Parental quality of life assessments report lower scores in single-parent homes but no differences were noted by race or parental employment status. CONCLUSIONS: Valuable information may be discerned from acute respiratory distress syndrome patients who return for follow-up evaluation. In this pilot study, up to one-third of children with acute respiratory distress syndrome exhibit pulmonary function deficits and 12-month postillness quality of life scores are lower than in children with chronic asthma. Parental perceptions of postillness quality of life may be negatively impacted by socioeconomic constraints. Long-term follow of children with acute respiratory distress syndrome is feasible and bears further investigation.

Management of plastic bronchitis with topical tissue-type plasminogen activator.

Plastic bronchitis or cast bronchitis is a rare disease of unclear etiology characterized by formation of airway casts that can lead to life-threatening airway obstruction. There is currently limited data regarding optimal treatment of plastic bronchitis. Several therapies have been suggested, but recurrences are common and mortality remains high. We report the case of a 6-year-old boy with refractory eosinophilic bronchial casts, unresponsive to low-dose systemic corticosteroids, inhaled corticosteroids, azithromycin, and dornase alfa, who was treated successfully and safely with direct instillation of tissue-type plasminogen activator (tPA) to the obstructing casts during flexible bronchoscopy and inhaled tPA. Our case illustrates that the current therapy for plastic bronchitis remains inadequate. To our knowledge, this case is the first to show that direct instillation of tPA can be used safely for treatment of this disease. The use of tPA via direct administration into the airways during bronchoscopy and via a nebulizer appeared to be a safe and effective therapy for plastic bronchitis and should be considered early in the course of the disease to prevent complications of severe airway obstruction.

The role of polysomnography in diagnosing and treating obstructive sleep apnea in pediatric patients.

Obstructive sleep apnea in children is associated with serious neurocognitive and cardiovascular morbidity, systemic inflammation, and increased health care use, yet remains underdiagnosed. Although the prevalence of obstructive sleep apnea is 1-3% in the pediatric population, the prevalence of primary snoring (PS) is estimated to be 3-12%. The challenge for pediatricians is to differentiate PS from obstructive sleep apnea in a cost-effective, reliable, and accurate manner before recommending invasive or intrusive therapies, such as surgery or continuous positive airway pressure. The validity of polysomnography as the gold standard for diagnosing obstructive sleep apnea has been challenged, primarily related to concerns that abnormalities on polysomnography do not correlate well with adverse outcomes, that those abnormalities have statistical more than clinical significance, and that performing polysomnograms on all children who snore is a practical impossibility. The aim of this article is to review the clinical utility of diagnostic tests other than polysomnography to diagnose obstructive sleep apnea, to highlight the limitations and strengths of polysomnography, to underscore the threshold levels of abnormalities detected on polysomnography that correlate with morbidity, and to discuss what the practical implications are for treatment.

Positive fluid balance is associated with higher mortality and prolonged mechanical ventilation in pediatric patients with acute lung injury.

Introduction. We analyzed a database of 320 pediatric patients with acute lung injury (ALI), to test the hypothesis that positive fluid balance is associated with worse clinical outcomes in children with ALI. Methods. This is a post-hoc analysis of previously collected data. Cumulative fluid balance was analyzed in ml per kilogram per day for the first 72 hours after ALI while in the PICU. The primary outcome was mortality; the secondary outcome was ventilator-free days. Results. Positive fluid balance (in increments of 10 mL/kg/24 h) was associated with a significant increase in both mortality and prolonged duration of mechanical ventilation, independent of the presence of multiple organ system failure and the extent of oxygenation defect. These relationships remained unchanged when the subgroup of patients with septic shock (n = 39) were excluded. Conclusions. Persistently positive fluid balance may be deleterious to pediatric patients with ALI. A confirmatory, prospective randomized controlled trial of fluid management in pediatric patients with ALI is warranted.

Blood product transfusions and clinical outcomes in pediatric patients with acute lung injury.

OBJECTIVE: There are data suggesting that blood product transfusions increase the risk of developing acute lung injury (ALI) in adults, and may be associated with increased mortality in adults with ALI. A possible association between transfusions and adverse outcomes of pediatric patients with ALI has not been studied previously. We tested the hypothesis that blood product transfusions to pediatric patients with ALI within the first 72 hours of the diagnosis would be associated with increased mortality and prolonged mechanical ventilation. DESIGN: An epidemiologic database of pediatric ALI prospectively gathered from July 1996 to May 2000 was analyzed. SETTING: Children were enrolled from both a tertiary referral hospital and a major community children's hospital. PATIENTS: Three hundred fifteen patients who met the 1994 American European Consensus Committee definition of ALI between the ages of 36 weeks corrected gestational age and 18 years. MAIN OUTCOME MEASURE: Mortality in the pediatric intensive care unit. RESULTS: Multivariate analyses indicated that the transfusion of fresh-frozen plasma (FFP) was associated with increased mortality, independent of the severity of hypoxemia (Pao2/Fio2), presence of multiple organ system failure or disseminated intravascular coagulation (odds ratio = 1.08, 95% confidence interval = 1.00-1.17, p = 0.04). FFP transfusion was analyzed as a continuous variable, so that for each milliliter of FFP transfused per kilogram patient body weight per day, the odds of death increased by 1.08. There was a trend toward an association of the transfusion of FFP with a fewer number of days of unassisted ventilation (regression coefficient = -0.21, 95% confidence interval = -0.42-0.01, p = 0.06). CONCLUSIONS: The transfusion of FFP is associated with an increased risk of mortality in children with ALI. The association between FFP and mortality in children with ALI should be investigated further.

Plasma receptor for advanced glycation end-products predicts duration of ICU stay and mechanical ventilation in patients after lung transplantation.

BACKGROUND: Primary graft dysfunction, formerly termed reperfusion pulmonary edema, is the leading cause of short-term complications after lung transplantation. New evidence shows that alveolar type I epithelial cells play an active role in alveolar fluid transport and are therefore presumed to be critical in the absorption of pulmonary edema. We tested the potential relevance of a novel marker of alveolar type I cell injury, the receptor for advanced glycation end-products (RAGE), to short-term outcomes of lung transplantation. METHODS: The study was a prospective, observational cohort study of 20 patients undergoing single lung, bilateral lung or combined heart-lung transplantation. Plasma biomarkers were measured 4 hours after allograft reperfusion. RESULTS: Higher plasma RAGE levels were associated with a longer duration of mechanical ventilation and longer intensive care unit length of stay, in contrast to markers of alveolar type II cell injury, endothelial injury and acute inflammation. Specifically, for every doubling in plasma RAGE levels, the duration of mechanical ventilation increased on average by 26 hours, adjusting for ischemia time (95% confidence interval [CI] 7.4 to 44.7 hours, p = 0.01). Likewise, for every doubling of plasma RAGE levels, intensive care unit length of stay increased on average by 1.8 days, again adjusting for ischemia time (95% CI 0.13 to 3.45 days p = 0.04). In contrast, the clinical diagnosis of primary graft dysfunction was not as predictive of these short-term outcomes. CONCLUSIONS: Higher levels of plasma RAGE measured shortly after reperfusion predicted poor short-term outcomes from lung transplantation. Elevated plasma RAGE levels may have both pathogenetic and prognostic value in patients after lung transplantation.

Biological markers of lung injury before and after the institution of positive pressure ventilation in patients with acute lung injury.

BACKGROUND: Several biological markers of lung injury are predictors of morbidity and mortality in patients with acute lung injury (ALI). The low tidal volume lung-protective ventilation strategy is associated with a significant decrease in plasma biomarker levels compared to the high tidal volume ventilation strategy. The primary objective of this study was to test whether the institution of lung-protective positive pressure ventilation in spontaneously ventilating patients with ALI exacerbates pre-existing lung injury by using measurements of biomarkers of lung injury before and after intubation. MATERIALS AND METHODS: A prospective observational cohort study was conducted in the intensive care unit of a tertiary care university hospital. Twenty-five intubated, mechanically ventilated patients with ALI were enrolled. Physiologic data and serum samples were collected within 6 hours before intubation and at two different time points within the first 24 hours after intubation to measure the concentration of interleukin (IL)-6, IL-8, intercellular adhesion molecule 1 (ICAM-1), and von Willebrand factor (vWF). The differences in biomarker levels before and after intubation were analysed using repeated measures analysis of variance and a paired t test with correction for multiple comparisons. RESULTS: Before endotracheal intubation, all of the biological markers (IL-8, IL-6, ICAM-1, and vWF) were elevated in the spontaneously breathing patients with ALI. After intubation and the institution of positive pressure ventilation (tidal volume 7 to 8 ml/kg per ideal body weight), none of the biological markers was significantly increased at either an early (3 +/- 2 hours) or later (21 +/- 5 hours) time point. However, the levels of IL-8 were significantly decreased at the later time point (21 +/- 5 hours) after intubation. During the 24-hour period after intubation, the PaO2/FiO2 (partial pressure of arterial oxygen/fraction of the inspired oxygen) ratio significantly increased and the plateau airway pressure significantly decreased. CONCLUSION: Levels of IL-8, IL-6, vWF, and ICAM-1 are elevated in spontaneously ventilating patients with ALI prior to endotracheal intubation. The institution of a lung-protective ventilation strategy with positive pressure ventilation does not further increase the levels of biological markers of lung injury. The results suggest that the institution of a lung-protective positive pressure ventilation strategy does not worsen the pre-existing lung injury in most patients with ALI.

Higher urine desmosine levels are associated with mortality in patients with acute lung injury.

Desmosine is a stable breakdown product of elastin that can be reliably measured in urine samples. We tested the hypothesis that higher baseline urine desmosine would be associated with higher mortality in 579 of 861 patients included in the recent Acute Respiratory Distress Syndrome Network trial of lower tidal volume ventilation (1). We also correlated urine desmosine levels with indexes of disease severity. Finally, we assessed whether urine desmosine was lower in patients who received lower tidal volumes. Desmosine was measured by radioimmunoassay in urine samples from days 0, 1, and 3 of the study. The data were expressed as a ratio of urine desmosine to urine creatinine to control for renal dilution. The results show that higher baseline (day 0) urine desmosine-to-creatinine concentration was associated with a higher risk of death on adjusted analysis (odds ratio 1.36, 95% confidence interval 1.02-1.82, P=0.03). Urine desmosine increased in both ventilator groups from day 0 to day 3, but the average rise was higher in the 12-ml/kg predicted body weight group compared with the 6-ml/kg predicted body weight group (P=0.053, repeated-measures model). In conclusion, patients with acute lung injury ventilated with lower tidal volumes have lower urine desmosine levels, a finding that may reflect reduced extracellular matrix breakdown. These results illustrate the value of evaluating urinary biological markers that may have prognostic and pathogenetic significance in acute lung injury.