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Objective Clinical diagnoses of asthma and reactive airway disease (RAD) in young children are subjective. We examined how often children were diagnosed with asthma versus RAD, and whether preventive care and 2-year clinical outcomes differed based on initial diagnosis. Methods We conducted a retrospective cohort analysis of children (2–7 years) from a university-based general pediatrics practice who had been diagnosed with RAD or asthma. We performed adjusted comparisons between groups for time until subsequent asthma-related care. We also compared delivery of asthma-related healthcare services, corticosteroid and controller prescriptions, and action plans within 2 years of index diagnosis, using bivariate and regression analyses. Results Four hundred three children were included (64% male, 67% Black, 25% Hispanic). RAD was diagnosed in 62% of index visits, and was more likely than asthma to be diagnosed in emergency settings. In the full sample, the time between index visit and subsequent asthma care did not differ between groups, after adjustment for index location. For subjects with complete 24-month follow-up (N = 300), no between-group differences were found in adjusted analyses. Most children with RAD received action plans and controller medications only after a subsequent asthma diagnosis, on average, 9 months after their index visit. Conclusions RAD diagnoses were linked to delayed delivery of preventive care measures, but within 2 years of initial diagnosis, clinical outcomes for those diagnosed with RAD and asthma did not differ. To facilitate clear communication and timely treatment, a prompt diagnosis of asthma, rather than RAD, should be considered for children with asthma symptoms.

BACKGROUND HIV-exposed uninfected (HEU) individuals are predisposed to adverse health outcomes, which in part may stem from the influence of an altered intrauterine milieu on fetal programming. The placenta serves as a readout for the effects of the maternal environment on the developing fetus and may itself contribute to the pathogenesis of disease. SETTING US academic health system. METHODS We leveraged a previously established registry-based cohort of HEU adolescents and young adults to identify 26 subjects for whom placental histopathology was available. We further obtained placental tissue from 29 HIV-unexposed pregnancies for comparison. We examined differences in placental histopathology between the groups and related villous vascularity in the HEU group to prenatal maternal characteristics and long-term health outcomes. RESULTS Placentas from HEU pregnancies demonstrated a higher blood vessel count per villus as compared with controls (5.9 ± 1.0 vs. 5.4 ± 0.8; P = 0.05), which was independent of maternal prenatal age, race, body mass index, smoking status, hemoglobin, and gestational age. Furthermore, within the HEU group, lower CD4+ T-cell count during pregnancy was associated with greater placental vascularity (r = -0.44; P = 0.03). No significant relationships were observed between placental blood vessel count per villus and body mass index z-score or reactive airway disease among HEU individuals later in life. CONCLUSIONS Placentas from HEU pregnancies demonstrated increased villous vascularity compared with HIV-unexposed controls in proportion to the severity of maternal immune dysfunction. Further studies are needed to examine intrauterine exposure to hypoxia as a potential mechanism of fetal programming in HIV.

The use of clinical scoring to assess for severity of respiratory distress and respiratory failure is challenging due to subjectivity and interrater variability. Transcutaneous Capnography (TcpCO2) can be used as an objective tool to assess a patient’s ventilatory status. This study was designed to assess for any correlation of continuous monitoring of TcpCO2 with the respiratory clinical scores and deterioration in children admitted for acute respiratory distress. A prospective observational study over one year on children aged 2 weeks to 5 years admitted with acute respiratory distress or failure secondary to Bronchiolitis and Reactive airway disease was performed. Continuous TcpCO2 monitoring for upto 48 h was recorded. Investigators, bedside physicians, respiratory therapists, and nurses were blinded from the transcutaneous trends at the time of data collection. Total of 813 TcpCO2 measurements at standard intervals of 30 min were obtained on 38 subjects. Subjects with abnormal TcpCO2 (> 45 mmHg) were younger (6.9 ± 5.2 vs. 23.05 ± 17.7 months,) and were more likely to be on higher oxygen flow rate (0.52 L/min/kg vs 0.46 lier/min/kg, p = 0.004) and higher FiO2 (38.4 vs 33.6, p

Case Presentation A 56-year-old man presented to the lung nodule clinic with abnormal chest imaging prompted by a chronic cough and hemoptysis. Approximately 2.5 years earlier, while kneeling beside his car fixing a flat tire, he fell backwards while holding the tire cap in his mouth, causing him to inhale sharply and aspirate the cap. He immediately developed an intractable cough productive of flecks of blood. He presented to an emergency room but left before being seen because of a long wait time and his lack of health-care insurance. He self-medicated for severe cough and chest discomfort with codeine, eventually developing a dependency. Approximately 3 weeks after aspirating the tire cap, his cough became productive, and he developed fever and chills. His symptoms improved transiently with antibiotics and additional narcotics. Ultimately, his chronic cough with intermittent hemoptysis affected his ability to work, and 30 months later he sought medical attention and was diagnosed with pneumonia and reactive airway disease. He was prescribed doxycycline, steroids, inhaled albuterol, and dextromethorphan, with initial improvement, but his symptoms recurred multiple times despite quitting smoking, leading to repeated medication courses.

Stem cells, including the resident lung mesenchymal stem cells (LMSCs), are critically important for injury repair. Compelling evidence links perinatal vitamin D (VD) deficiency to reactive airway disease; however, the effects of perinatal VD deficiency on LMSC function is unknown. We tested the hypothesis that perinatal VD deficiency alters LMSC proliferation, differentiation, and function, leading to an enhanced myogenic phenotype. We also determined whether LMSCs' effects on alveolar type II (ATII) cell function are paracrine. Using an established rat model of perinatal VD deficiency, we studied the effects of four dietary regimens (0, 250, 500, or 1,000 IU/kg cholecalciferol-supplemented groups). At Postnatal Day 21, LMSCs were isolated, and cell proliferation and differentiation (under basal and adipogenic induction conditions) were determined. LMSC paracrine effects on ATII cell proliferation and differentiation were determined by culturing ATII cells in LMSC-conditioned media from different experimental groups. Using flow cytometry, >95% of cells were CD45-ve, >90% were CD90 + ve, >58% were CD105 + ve, and >64% were Stro-1 + ve, indicating their stem cell phenotype. Compared with the VD-supplemented groups, LMSCs from the VD-deficient group demonstrated suppressed PPARγ, but enhanced Wnt signaling, under basal and adipogenic induction conditions. LMSCs from 250 VD- and 500 VD-supplemented groups effectively blocked the effects of perinatal VD deficiency. LMSC-conditioned media from the VD-deficient group inhibited ATII cell proliferation and differentiation compared with those from the 250 VD- and 500 VD-supplemented groups. These data support the concept that perinatal VD deficiency alters LMSC proliferation and differentiation, potentially contributing to increased respiratory morbidity seen in children born to mothers with VD deficiency.

Background HIV-negative individuals with in utero HIV exposure represent an emerging population, exceeding 18 million people worldwide. Long-term clinical outcomes among HIV-exposed uninfected (HEU) individuals into adolescence and young adulthood remain unknown. Setting US academic health system. Methods In this observational cohort study, we leveraged a patient data registry to identify 50 HEU adolescents and young adults. We also identified 141 HIV-unexposed controls that were matched to HEU subjects up to 3:1 on age of last encounter (±2 years), birthdate (±5 years), sex, race/ethnicity, and zip code. All subjects were born since January 1, 1990, with medical records available into adolescence and young adulthood. Primary outcomes were most recent body mass index (BMI) z-score and presence of reactive airway disease (RAD). Records were manually reviewed to extract health information. Results Fifty HEU adolescents and young adults (18 ± 3 years, 54% men) and 141 matched controls (19 ± 3 years, 54% men) were compared. HEU individuals had a higher BMI z-score (1.12 ± 1.08 vs. 0.73 ± 1.09, P = 0.03) and an increased prevalence of obesity (42% vs. 22%, P = 0.009) compared with controls. HEU subjects also had a higher prevalence of RAD vs. controls (40% vs. 23%, P = 0.03). These differences persisted on adjusting for demographic, socioeconomic, maternal, and birth-related factors. Maternal prenatal CD4 T-cell count was inversely associated with BMI z-score among HEU adolescents (r = -0.47, P = 0.01). Conclusions HEU adolescents and young adults exhibited a heightened prevalence of obesity and RAD compared with HIV-unexposed controls. Additional studies are needed to optimize care for the expanding population of HEU individuals transitioning to adulthood.

Follicular bronchiolitis (FB) is a rare bronchiolar disorder associated with hyperplasia of the bronchial-associated lymphoid tissue (BALT). It is characterized by the development of lymphoid follicles with germinal centers in the walls of small airways. It falls under the category of lymphoproliferative pulmonary diseases (LPDs) and commonly occurs in relation to connective tissue disease, immunodeficiency, infections, interstitial lung disease (ILD), and inflammatory airway diseases. Computerized tomography (CT) findings include centrilobular nodules with patchy ground glass infiltrate, tree-in-bud findings, and air trapping. It can very rarely present as diffuse cystic lung disease. We present two cases of FB. The first case is associated with Human Immunodeficiency Virus (HIV) infection and asthma with diffuse cystic changes on the CT. The second case is associated with reactive airway disease and gastroesophageal reflux disease (GERD) with the classic centrilobular nodules and ground glass opacities on the CT.

Reactive airway disease is a prevalent condition that can be detected in the early infancy period. The condition might also deteriorate into asthma in some cases. If infants do not respond to the treatment of persistent wheeze and coughing, other rare causes should be investigated. The complete form of vascular ring is an extremely uncommon congenital cardiovascular abnormality. Double aortic arch constitutes the most significant portion of the complete vascular ring anomalies. Clinical manifestations of the anomaly are mainly respiratory due to the tracheal compression and mimicking the conditions of asthma. There have not been many reports about the clinical presentations of double aortic arch being remarkably similar to the same clinical manifestations of asthma in the literature. As far as we can be sure, there have not been any reported cases about severe reactive airway disease that caused a patient to have a life-threatening condition in the pediatric intensive care unit. Herein, we present a 5-month-old girl who had double aortic arch. Her anatomical aberration was diagnosed by three-dimensional computed tomography angiography of thorax, and the anomaly mimicked the clinical characteristics of life-threatening severe reactive airway disease.

Supplemental O2 (hyperoxia; 30-90% O2) is a necessary intervention for premature infants, but it contributes to development of neonatal and pediatric asthma, necessitating better understanding of contributory mechanisms in hyperoxia-induced changes to airway structure and function. In adults, environmental stressors promote formation of senescent cells that secrete factors (senescence-associated secretory phenotype), which can be inflammatory and have paracrine effects that enhance chronic lung diseases. Hyperoxia-induced changes in airway structure and function are mediated in part by effects on airway smooth muscle (ASM). In the present study, using human fetal ASM cells as a model of prematurity, we ascertained the effects of clinically relevant moderate hyperoxia (40% O2) on cellular senescence. Fetal ASM exposed to 40% O2 for 7 days exhibited elevated concentrations of senescence-associated markers, including β-galactosidase; cell cycle checkpoint proteins p16, p21, and p-p53; and the DNA damage marker p-γH2A.X (phosphorylated γ-histone family member X). The combination of dasatinib and quercetin, compounds known to eliminate senescent cells (senolytics), reduced the number of hyperoxia-exposed β-galactosidase-, p21-, p16-, and p-γH2A.X-positive ASM cells. The senescence-associated secretory phenotype profile of hyperoxia-exposed cells included both profibrotic and proinflammatory mediators. Naive ASM exposed to media from hyperoxia-exposed senescent cells exhibited increased collagen and fibronectin and higher contractility. Our data show that induction of cellular senescence by hyperoxia leads to secretion of inflammatory factors and has a functional effect on naive ASM. Cellular senescence in the airway may thus contribute to pediatric airway disease in the context of sequelae of preterm birth.

Kawasaki disease (KD), particularly incomplete form, might present with wide spectrum clinical features. The treatment regimen includes a combination of intravenous immunoglobulins (IVIG) and aspirin. The use of steroids has been studied as an adjunctive therapy and its role in preventing coronary artery (CA) complications is still debatable. Here, we are presenting a rare presentation of incomplete KD. A previously healthy 5-year-old Arab girl, presented with clinical features consistent with pneumonia, rash, and enlarged cervical lymph nodes. On admission, antibiotics were administered intravenously in addition to steroids considering her reactive airway disease history which resulted in interim improvement. Yet, upon clinical worsening, her clinical status was revised, laboratory and physical examination revealed raised inflammatory markers, new opacity of pulmonary consolidation on chest X-ray, and peeling of skin. Because of high clinical suspicion of incomplete KD combined with her echocardiography that showed prominent coronary arteries, diagnosis of incomplete KD was made. After treating her with IVIG and aspirin, the patient made a full recovery. We are reporting pneumonia-like presentation of incomplete KD. High index of suspicion is required to diagnosis and treat promptly to prevent complications.

Background Pneumonia in infancy has been linked to long-term consequences for the rapidly developing lung. We examined the impact of hospitalized community-acquired pneumonia (CAP) on subsequent respiratory health. Methods We conducted a retrospective matched-cohort study using the Optum® de-identified Electronic Health Record Dataset (2009-2018). Study population comprised healthy infants hospitalized for CAP (“CAP patients”), and matched comparators without pneumonia (“comparison patients”), before age 2 years. Study outcomes included any chronic respiratory disorder, reactive airway disease (asthma, hyperactive airway disease, recurrent wheezing), and CAP hospitalization occurring between age 2 to 5 years, and were evaluated overall as well as by age and etiology at first CAP hospitalization. Results Study population totaled 1,343 CAP patients and 6,715 comparison patients. Rates per 100 patient-years and relative rates (RR) of study outcomes from age 2 to 5 years for CAP patients versus comparison patients were: any chronic respiratory disorder, 11.6 vs. 4.9 (RR=2.4 [95% CI: 2.1-2.6]); reactive airway disease, 6.1 vs 1.9 (RR=3.2 [2.6-3.8]); and CAP hospitalization, 1.0 vs 0.2 (RR=6.3 [3.6-10.9]). Rates of study outcomes were highest among CAP patients who had their initial hospitalization in the second year of life. Conclusions Infant CAP foreshadows an increased risk of subsequent chronic respiratory disorders, which may be elevated when CAP occurs closer to pre-school age (i.e., age 2 to 5 years). These findings are most consistent with the hypothesis that inflammation persists beyond the acute stage of pneumonia and plays a role in the development of chronic respiratory sequelae.

BackgroundDiagnostic errors are a global health priority and a common cause of preventable harm. There is limited data available for the prevalence of misdiagnosis in pediatric acute-care settings. Respiratory illnesses, which are particularly challenging to diagnose, are the most frequent reason for presentation to pediatric emergency departments.ObjectiveTo determine the diagnostic error rate of acute childhood respiratory diseases in emergency departments.MethodsProspective, multicenter, single-blinded, diagnostic accuracy study in two well-resourced pediatric emergency departments in a large Australian city. Between September 2016 and August 2018, a convenience sample of children aged 29 days to 12 years who presented with respiratory symptoms was enrolled. The emergency department discharge diagnoses were reported by clinicians based upon standard clinical diagnostic definitions. These diagnoses were compared against consensus diagnoses given by an expert panel of pediatric specialists using standardized disease definitions after they reviewed all medical records.ResultsFor 620 participants, the positive and negative percent agreement (%, [95% CI]) of the emergency department compared with the expert panel diagnoses were generally poor: isolated upper respiratory tract disease (61.4 [51.2, 70.9], 90.9 [88.1, 93.3]), croup (75.6 [64.9, 84.4], 97.9 [96.2, 98.9]), lower respiratory tract disease (86.4 [83.1, 89.6], 92.9 [87.7, 96.4]), bronchiolitis (66.9 [58.6, 74.5], 94.3 [80.8, 99.3]), asthma/reactive airway disease (91.0 [85.8, 94.8], 93.0 [90.1, 95.3]), clinical pneumonia (62·9 [49·7, 74·8], 95·0 [92·8, 96·7]), focal (consolidative) pneumonia (54·8 [38·7, 70·2], 86.2 [79.3, 91.5]). Only 59% of chest x-rays with consolidation were correctly identified. Between 6.9% and 14.5% of children were inappropriately prescribed based on their eventual diagnosis.ConclusionIn well-resourced emergency departments, we have identified a previously unrecognized high diagnostic error rate for acute childhood respiratory disorders, particularly in pneumonia and bronchiolitis. These errors lead to the potential of avoidable harm and the administration of inappropriate treatment.

A previously healthy 15-year-old boy from a rural county in the southeastern United States was evaluated in the emergency department with fever and worsening toe pain in the absence of trauma. He initially presented to his primary care physician 4 weeks before with upper respiratory symptoms and was treated with corticosteroids for presumed reactive airway disease. His respiratory symptoms resolved. One week after this presentation, he developed fever and right great toe pain and presented to an outside hospital. Inflammatory markers were elevated. MRI confirmed a diagnosis of osteomyelitis with associated periosteal abscess. He was treated with intravenous antibiotics and drainage of the abscess. Ten days after his discharge from the outside hospital, he developed fever and had increasing drainage of the toe and pain refractory to oral pain medications. He presented to our facility for further evaluation. Repeat MRI and inflammatory markers corroborated his worsening disease, and he was admitted to the hospital for intravenous antibiotics and underwent serial surgical debridement. He developed painful subcutaneous nodules on his lower extremities and was found to have lung abnormalities on chest radiograph. A multispecialty team collaborated in the management of this patient and unveiled a surprising diagnosis.

Pediatric patients with respiratory signs and symptoms who are found to be wheezing present a diagnostic dilemma to pediatricians. The majority of these cases are diagnosed as some degree of reactive airway disease, either as viral bronchiolitis or asthma. In this scenario, a patient with wheezing was initially given 2 courses of appropriate antibiotics on the basis of the duration and concurrence of other symptoms. However, he was subsequently referred to a pediatric pulmonologist for further workup after failure to improve and persistent oxygen saturations in the low-to-mid 90s. More extensive testing was completed by the pediatric pulmonologist, in addition to a short hospital admission. A rigid bronchoscopy was eventually completed, which revealed small pieces of partially digested material. Although his persistent cough resolved, his saturations continued to be suboptimal. A chest computed tomography scan with contrast was then completed, which eventually led to his diagnosis and appropriate treatment and resolution of his symptoms.

Double aortic arch (DAA) is a common form of complete vascular ring. The condition leads to airway obstruction and compression of the esophagus. A balanced type of DAA is an extremely rare anomaly. The anatomical aberration cannot be easily distinguished by transthoracic echocardiography when an infant has chronic respiratory distress. Herein we presented a case of an 11-month-old infant who had chronic respiratory distress and a balanced type of DAA.

Inhaled mometasone was shown to improve pain scores and decrease soluble vascular cell adhesion molecule (sVCAM) concentration in a randomized controlled trial of nonasthmatic patients with sickle cell disease. We sought to explore potential changes in systemic inflammation as a mechanism underlying this effect. Serum samples from 41 trial participants (15 placebo- and 26 mometasone-treated) were analyzed using a 92 inflammatory marker panel at baseline and after 8 weeks of mometasone therapy. Individual marker analysis and correlation analysis were conducted. Adjusted for age, the mometasone-treated group decreased the concentration of CXCL9, CXCL11, CD40, IL-10, and IL-18 relative to placebo-treated participants. Hierarchical clustering and correlation analysis identified additional evidence for a decrease in cytokines linking to macrophage signaling and migration. There was no statistically significant change in markers of asthma and allergy, indicating that the improvement was unlikely mediated by modulation of occult reactive airway disease. This analysis of inflammatory markers suggests that decrease in macrophage activity may be involved in the mediation of the clinical benefit seen with use of inhaled mometasone in nonasthmatic patients with sickle cell disease. Trial registration: clinicaltrials.gov identifier: NCT02061202.

Background Rhinoviruses (RVs) are ubiquitous respiratory pathogens that often cause mild or subclinical infections. Molecular detection of RVs from the upper respiratory tract can be prolonged, complicating etiologic association in persons with severe lower respiratory tract infections. Little is known about RV viremia and its value as a diagnostic indicator in persons hospitalized with community-acquired pneumonia (CAP). Methods Sera from RV-positive children and adults hospitalized with CAP were tested for RV by real-time reverse-transcription polymerase chain reaction. Rhinovirus species and type were determined by partial genome sequencing. Results Overall, 57 of 570 (10%) RV-positive patients were viremic, and all were children aged