Lockdown Fatigue in Pediatric Respiratory Patients: Lessons from the First COVID-19 Year.

Lockdown policies have been implemented worldwide to limit the spread of COVID-19. "Lockdown fatigue" is a state of exhaustion related to the accumulating effects of repeated lockdowns. The aim of the current study was to examine the effects of repeated lockdowns on children with respiratory disorders. Data on children aged 0−18 years old with respiratory disorders were collected by an electronic survey during the third lockdown in Israel. The retrieved information included demographics and baseline medical status, respiratory clinical status during the third lockdown compared to pre-lockdown periods, lockdown adherence, lifestyle modifications and caregiver emotional status. The results were compared to those of a similar questionnaire distributed during the first lockdown. A total of 234 patients (62% males, 37% females, mean age 6.8 years (confidence interval 6.1−7.5)) were enrolled. Respiratory symptoms and exacerbation frequency were reduced in 76 (35.5%) and 58 (27.4%) patients, respectively, compared to the pre-lockdown period and similar to the first lockdown (p = 0.840 and p = 0.063, respectively). However, compared to the first lockdown, the third lockdown was associated with greater use of reliever medications (p = 0.006), less use of inhaled corticosteroids as routine treatment (p = 0.027), and more pediatric emergency room visits and hospitalizations (p = 0.001 and p < 0.001, respectively). The results also showed an increase in sedentary lifestyle (e.g., reduced physical activity (p = 0.025), less healthy eating habits (p = 0.001)) and reduced adherence to lockdown policies (p < 0.001). These data show that the continuing stability of clinical improvement during lockdown was accompanied by deleterious sequelae that potentially indicate "lockdown fatigue" among children with respiratory disorders.

Asthma risk after a pediatric intensive care unit admission for respiratory syncytial virus bronchiolitis.

BACKGROUND: Admission to a pediatric intensive care unit (PICU) has been associated with respiratory consequences in children with asthma and carries major implications for management control. Whereas respiratory syncytial virus (RSV) bronchiolitis has been associated with increasing intensity of wheezing, the relationship between RSV-bronchiolitis PICU admission and future asthma is unclear. This retrospective case-control study evaluated whether hospitalization in the PICU due to RSV bronchiolitis is more likely to be associated with future asthma in early life compared with hospitalization in a general pediatric ward. METHODS: Children hospitalized due to RSV bronchiolitis between 2007 and 2019 in the PICU (study group) were compared to those hospitalized in a general pediatric ward (controls). Asthma prevalence was assessed by a follow-up questionnaire based on The International Study of Asthma and Allergies in Childhood questionnaire. RESULTS: Sixty-three PICU patients and 66 controls were included. The PICU patients presented with more severe disease during RSV hospitalization. At follow-up, significantly more PICU patients aged 3-6 years had physician-diagnosed asthma, respiratory symptoms during the previous 12 months, and underwent respiratory treatment since hospital discharge compared to controls (14 [60.9%] vs. 4 [18.2%] patients; 15 [65.2%] vs. 6 [27.3%]; and 16 [69.6%] vs. 8 [36.4%]; respectively). These differences were no longer observed after 6 years of age. CONCLUSIONS: Children admitted to the PICU for RSV bronchiolitis are at higher risk for asthma in subsequent pre-school years and will require close respiratory follow-up than those admitted to general pediatric wards. Admission venue should be queried when asthma is suspected.

Fractional exhaled Nitric Oxide (FeNO) level as a predictor of COVID-19 disease severity.

OBJECTIVE: To assess the feasibility of Fractional exhaled Nitric Oxide (FeNO) as a simple, non-invasive, cost-effective and portable biomarker and decision support tool for risk stratification of COVID-19 patients. METHODS: We conducted a single-center prospective cohort study of COVID-19 patients whose FeNO levels were measured upon ward admission by the Vivatmo-me handheld device. Demographics, COVID-19 symptoms, and relevant hospitalization details were retrieved from the hospital databases. The patients were divided into those discharged to recover at home and those who died during hospitalization or required admission to an intensive care unit, internal medicine ward, or dedicated facility (severe outcomes group). RESULTS: Fifty-six patients were enrolled. The only significant demographic difference between the severe outcomes patients (n = 14) and the home discharge patients (n = 42) was age (64.21 ± 13.97 vs. 53.98 ± 15.57 years, respectively, P = .04). The admission FeNO measurement was significantly lower in the former group compared with the latter group (15.86 ± 14.74 vs. 25.77 ± 13.79, parts per billion [PPB], respectively, P = .008). Time to severe outcome among patients with FeNO measurements ≤11.8 PPB was significantly shorter compared with patients whose FeNO measured >11.8 PPB (19.25 ± 2.96 vs. 24.41 ± 1.09 days, respectively, 95% confidence interval [CI] 1.06 to 4.25). An admission FeNO ≤11.8 PPB was a significant risk factor for severe outcomes (odds ratio = 12.8, 95% CI: 2.78 to 58.88, P = .001), with a receiver operating characteristics curve of 0.752. CONCLUSIONS: FeNO measurements by the Vivatmo-me handheld device can serve as a biomarker and COVID-19 support tool for medical teams. These easy-to-use, portable, and noninvasive devices may serve as valuable ED bedside tools during a pandemic.

Unforeseen changes in seasonality of pediatric respiratory illnesses during the first COVID-19 pandemic year.

OBJECTIVES: To investigate whether the three nationwide coronavirus disease 2019 (COVID-19) lockdowns imposed in Israel during the full first pandemic year altered the traditional seasonality of pediatric respiratory healthcare utilization. METHODS: Month by month pediatric emergency department (ED) visits and hospitalizations for respiratory diagnoses during the first full COVID-19 year were compared to those recorded for the six consecutive years preceding the pandemic. Data were collected from the patients' electronic files by utilizing a data extraction platform (MDClone© ). RESULTS: A significant decline of 40% in respiratory ED visits and 54%-73% in respiratory hospitalizations during the first COVID-19 year compared with the pre-COVID-19 years were observed (p < 0.001 and p < 0.001, respectively). The rate of respiratory ED visits out of the total monthly visits, mostly for asthma, peaked during June 2020, compared with proceeding years (109 [5.9%] versus 88 [3.9%] visits; p < 0.001). This peak occurred 2 weeks after the lifting of the first lockdown, resembling the "back-to-school asthma" phenomenon of September. CONCLUSIONS: This study demonstrates important changes in the seasonality of pediatric respiratory illnesses during the first COVID-19 year, including a new "back-from-lockdown" asthma peak. These dramatic changes along with the recent resurgence of respiratory diseases may indicate the beginnings of altered seasonality in pediatric pulmonary pathologies as collateral damage of the pandemic.

A case of an unfortunate tooth fairy visit to a ventilator-dependent child.

An 8-year-old boy recently sustained a cerebellar arteriovenous malformation rupture, and subsequently suffered from severe neurological injury and became ventilator-dependent through a tracheostomy. During a routine clinic visit, the parents reported that a loose baby tooth had fallen out and disappeared 7 days earlier. The physical examination was unremarkable, but a chest X-ray demonstrated a foreign body in the left lung and secondary atelectasis. A rigid bronchoscopy extracted what turned out to be a tooth from the left lower lobe bronchus, with no associated sequelae. Aspiration of a tooth is rare, and it is mostly seen in children and elderly patients following trauma, endotracheal intubation, and dental procedures. Only a few previous studies emphasized the increased risk of foreign body aspiration among neurological impaired children. This unique report describes a child in his physiological exfoliation period, which is characterized by the spontaneous shedding of 20 teeth over the course of several years. In severely neurologically impaired children, this period carries a risk of aspiration of teeth and secondary pulmonary damage. Therefore, treating physicians and caregivers must be aware of this risk, and routine dental check-ups are advised in a neurological impaired child during this period.

Nonrespiratory complications of nusinersen-treated spinal muscular atrophy type 1 patients.

BACKGROUND: Emergence of new treatments for spinal muscular atrophy type 1 (SMA1) has led to dramatic improvements in respiratory failure and survival. However, these "treated" patients sustain major problems in other organ systems, which may directly or indirectly affect their respiratory function. We observed three main nonrespiratory manifestations in these patients comprised of facial deformities, feeding problems, and spinal deformities. OBJECTIVE: To investigate these three main sequelae in nusinersen-treated SMA1 patients. METHODS: Data on nusinersen-treated SMA1 patients were prospectively collected throughout a 3-year period, with special focus upon nonrespiratory features of the disease. RESULTS: Twenty nusinersen-treated SMA1 patients were included (eight males, median age 13.5 months, interquartile range: 4-56.2 months), among whom 17 survived after 3 years of follow-up. At follow-up, 15 (88%) patients were diagnosed with facial weakness, hypoplasia, or deformity. All but one patient (94%) were fed invasively by percutaneous endoscopic gastrostomy or nasogastric tube feeding. Four patients (25%) had maintained oral feeding in parallel to gastrostomy feeding and had clinical and radiologic evidence of aspirations. Fifteen (88%) patients were diagnosed with scoliosis, of whom seven had undergone or were scheduled to undergo corrective surgery. CONCLUSIONS: Nusinersen-treated SMA1 patients may sustain facial deformities, feeding problems, and severe scoliosis, all of which affect their respiratory system. Strict surveillance of these complications is essential to avoid further respiratory morbidity.

Respiratory syncytial virus bronchiolitis among refugees and asylum seekers from war-torn countries.

BACKGROUND: Bronchiolitis is a prominent illness in children with a high burden in the developing world. Our objective was to assess bronchiolitis severity among infants and toddlers of refugees and asylum seekers who fled from developing countries with high disease burden to a developed country. STUDY DESIGN: A retrospective cohort comparative-group study of children 0-24 months of age who were admitted with a diagnosis of respiratory syncytial virus (RSV) bronchiolitis to a tertiary university-affiliated medical center during 2009-2017. The refugees and asylum seekers (study group) were mostly from war-torn African countries, and the control group was comprised of children from Israel (controls), a developed country. The primary outcome was length of stay (LOS), and the secondary outcomes were nutritional support and disease characteristics. RESULTS: A total of 185 patients were included (92 refugees and 93 controls). The mean LOS was higher for the former compared to the latter (4.7 ± 3.2 vs. 3.5 ± 2 days, respectively, p = .004). More hospitalized refugees required nutritional support compared to controls (48% vs. 24%, respectively, p = .002). No differences were found in vital signs, physical findings and symptoms, laboratory results, or complications. CONCLUSIONS: Refugees and asylum seekers from developing countries presented with a longer RSV bronchiolitis disease course and required more nutritional support compared to their Israeli counterparts. This may suggest a more severe disease.

Real-time effects of COVID-19 pandemic lockdown on pediatric respiratory patients.

OBJECTIVE: A national lockdown was implemented in Israel to slow the viral spread of COVID-19. We assessed the real-time effects of the lockdown on disease expression and lifestyle modifications in pediatric patients with chronic respiratory disorders. METHODS: An anonymous electronic questionnaire was distributed during lockdown (March-May 2020) to caregivers of patients with chronic respiratory disorders. The primary outcome was change in disease expression and the secondary outcomes were changes in lifestyle and caregivers' emotional status. RESULTS: The clinical status of one-third of the 445 participating patients (age 0-18 years) reportedly improved, including decreased respiratory symptoms (n = 133, 33%), exacerbation frequency (n = 147, 35%), and use of reliever medications (n = 101, 27.4%). The condition of ~10% of the patients worsened. Clinical improvement was noted mostly in young patients <5 years (p = .001), asthmatic patients (p = .033), and patients with multiple underlying respiratory disorders (p = .015). Patients whose condition significantly worsened were more likely to be >5 years (p < .001), had increased screen time, decreased physical activity, and shorter sleep duration compared to their younger counterparts (p = .008, <.001, and .001, respectively). Caregivers' reports (n = 236 [58%]) of their own anxiety levels and perceptions of the patients' elevated health risk were increased, regardless of the children's actual clinical status. CONCLUSION: COVID-19 lockdown was associated with clinical improvement/stability for most of the surveyed children; however, their caregivers' anxiety level was heightened. An increased sedentary lifestyle was reported mostly in older children.

High fractional exhaled nitric oxide levels in asthma patients: Does size matter?

BACKGROUND: Fractional exhaled nitric oxide (FeNO) is a biomarker for eosinophilic inflammation used for diagnosis and monitoring of asthma. High FeNO indicates significant airway eosinophilia and steroid-responsive airway inflammation. Some children with asthma have extremely high FeNO levels, but whether these levels represent a different asthma phenotype compared with those with mildly elevated FeNO is unclear. The objective of this study is to investigate whether the extent of high FeNO levels correlates with clinical phenotype, asthma control, comorbidity, and pulmonary function test (PFT) findings in children with asthma. METHODS: Anthropometric data, daytime and nighttime symptoms, controller treatment, comorbidity, and PFT findings were retrieved from the Pediatric Pulmonology Unit database (2014-2020) and correlated with FeNO levels in pediatric asthma patients with high FeNO levels. RESULTS: Two-hundred children and adolescents with high FeNO levels (range 36-227 ppb) were included. Within this range, higher FeNO levels positively correlated with increased daytime and nighttime symptoms (p = .013 and p = .01, respectively) and poorly controlled asthma (p = .034). A FeNO level of ≥80 ppb was the cutoff for significantly more severe daytime and nighttime symptoms and very poorly controlled asthma compared with levels <80 ppb (p = .004, p = .005, and p = .036, respectively). No correlation was found between FeNO and controller treatment, comorbidity, and PFT performance. CONCLUSION: In pediatric asthma patients, high FeNO levels correlate with increased symptom severity and poor asthma control. A FeNO level of ≥80 ppb may serve as an objective indicator for severe asthma.

Nusinersen for spinal muscular atrophy type 1: Real-world respiratory experience.

BACKGROUND: The emergence of new treatments for spinal muscular atrophy (SMA) is revolutionary, especially for SMA type 1 (SMA1). Data on respiratory outcomes remain sparse and rely mostly on randomized clinical trials. We report our experience of Nusinersen-treated SMA1 patients in real-world settings. METHODS: Data from SMA1 patients treated with Nusinersen were prospectively collected between 1/2017 and 1/2020. Respiratory variables included the use of assisted ventilation, the use of mechanical insufflation-exsufflation (MIE), respiratory complications, and death or treatment cessation due to respiratory reasons. RESULTS: Twenty SMA1 patients were assessed before and after 2 years of Nusinersen treatment which was initiated at a median age of 13.5 months (range, 1-184). At baseline, 16 patients were using assisted ventilation, eight noninvasive and eight invasive. Twelve patients were using permanent ventilation and four partial ventilation. After 2 years of treatment, there was no change in respiratory support among ventilated patients. All four patients who were free from respiratory support at baseline required the initiation of assisted ventilation during the study period. All 20 patients used MIE after 2 years of treatment. Two patients died from acute respiratory failure and one sustained severe brain injury. Four patients had chronic and/or recurrent atelectasis. CONCLUSION: Most of our patients were stable in their need for assisted ventilation and did not worsen as expected in SMA1, nor did they improve as might be hoped. Future studies are needed to determine if earlier treatment with Nusinersen might result in respiratory outcomes superior to those reported in this real-life study.

The Effect of Physical Activity on Human Milk Macronutrient Content and Its Volume.

Objective: There are multiple health benefits associated with both breastfeeding and practicing physical activity (PA). Therefore, it is likely that many women might want to engage in both. We designed the current randomized clinical trial to examine the effect of moderate- to high-intensity PA on human milk (HM) volume and macronutrient contents. Methods and Study Design: In this prospective, randomized, crossover clinical trial, we recruited 31 healthy mothers who had been exclusively breastfeeding their infants. Mothers expressed HM twice each day on 2 consecutive days-a day with PA (1-hour before and 1-hour after PA) and a control day without PA (at the exact same hours of the day). The order of days (with/without PA) was determined randomly. Macronutrients and energy contents of HM were analyzed using the Human Milk Analyzer (Miris AB, Uppsala, Sweden). PA was graded according to the Borg Rating of Perceived Exertion scale (RPE scale). Results: A total 124 HM samples from 31 mothers were analyzed. Moderate- to high-intensity PA affected neither macronutrients (fat, carbohydrates, protein) nor energy content. Milk volume remained unaffected by PA as well. Conclusions: Maternal PA does not affect HM volume or its macronutrient contents. Lactating mothers can be reassured regarding their breast milk volume and composition while practicing PA of moderate to high intensity.