key: cord-336562-5qmzne98 authors: Auten, Richard; Ren, Clement; Yilmaz, Ozge; Noah, Terry L. title: Pediatric pulmonology year in review 2016: Part 2 date: 2017-04-25 journal: Pediatr Pulmonol DOI: 10.1002/ppul.23719 sha: doc_id: 336562 cord_uid: 5qmzne98 Pediatric Pulmonology continues to publish research and clinical topics related to the entire range of children's respiratory disorders. As we have done annually in recent years, we here summarize some of the past year's publications in our major topic areas, as well as selected literature in these areas from other core journals relevant to our discipline. This review (Part 2) covers selected articles on neonatology, asthma, physiology and lung function testing, and infectious diseases. Pediatric Pulmonology continues to publish research and clinical topics related to the entire range of children's respiratory disorders. As we have done annually in recent years, we here summarize some of the past year's publications in our major topic areas, as well as selected literature in these areas from other core journals relevant to our discipline. This review (Part 2) covers selected articles on neonatology, asthma, physiology and lung function testing, and infectious diseases. Since mechanical ventilation inevitably exposes the developing respiratory system to unpredictable mechanical strains and stresses, clinicians have long sought safer and less invasive approaches to respiratory support, and better tools with which to monitor respiratory function during intensive care. There has been a trend to substitute high flow nasal cannulae which are able to deliver positive pressure, but this pressure is typically not regulated or monitored. In an effort to define the limitations of this approach, Gerdes et al 1 identified factors affecting delivered mean airway pressure during nasal CPAP delivery with the RAM™ cannula, an increasingly widely used device favored by some because of its apparent toleration compared with other devices that require more complex fixation systems. Using a polymer model of the upper airway and lip, RAM cannulae, and corresponding standard nCPAP prongs were affixed and delivered pressures measured using a pneumotachograph. As expected, complete occlusion of the nasal passage with either the RAM cannula or "standard" nasal prongs delivered comparable pressures that approximated the set pressure, providing that the RAM cannula was fully inserted. However, the authors point out a critical limitation to using the RAM cannula, namely that nasal expiratory resistance will be quite high if the nares are occluded. For babies that must be managed with mechanical ventilation, efforts are underway to improve both delivery and accurate monitoring of therapy. The safe use of high-frequency ventilation in newborns limits the ability of the clinician to assess ventilation in realtime. Minute ventilation and tidal volume cannot be measured, and capnography has been limited to transcutaneous CO 2 measurements, which have been problematic in very premature newborns that may not tolerate the skin temperatures that until very recently have been required for accurate measurement. Kugelman et al 2 evaluated capnography using a 2-lumen endotracheal tube and microstream capnography correlated with arterial blood gas measurements obtained from an indwelling line. Although accuracy was not acceptable, capnography was able to predict very low P a CO 2 < 30 Torr and very high P a CO 2 above 60 Torr. Respiratory volumes can also be assessed non-invasively using electrical impedance. Van findings with their earlier reports of increased methacholine induced respiratory system resistance. 11 The evidence for human susceptibility to neonatal and early childhood pulmonary insults that affect lung function in adulthood continues to mount, as reviewed by Goldizen et al. 12 Impairments of small airway function were reported by Verheggen et al, 13 reporting a case-control comparison of pulmonary function testing in 4-to 8-year old subjects born before 32 weeks with or without BPD. They used forced oscillometry or spirometry. They reported that pulmonary reactance, an oscillometric method used to assess small airway function, was worse in BPD subjects. Although this finding is not surprising, it should be tempered by the relatively low recruitment rate they experienced from their original qualifying cohort. Factors associated with BPD risk like duration of oxygen exposure and male sex were also associated with increased pulmonary reactance. The genetic basis of asthma has been investigated in many studies recently. Hua et al 14 investigated the gene-gene interactions among variants of the IL13, IL4, IL4RA, FCER1B, and ADRB2 genes, which have been associated with asthma in children, and demonstrated that single nucleotide polymorphisms IL13 rs20541, IL4 rs2243250, ADRB2 rs1042713n, and FCER1B rs569108 were associated with asthma. Moreover, risk of asthma was increased more than 10 times in carriers of all four risk homozygotes (IL13 rs20541 GG, IL4 rs2243250 TT, ADRB2 rs1042713 AA, and FCER1B rs569108 GG). These results add to the evidence for a role for epigenetic mechanisms in the relationship between environmental smoke exposure during pregnancy and pediatric asthma. Gene-environment interaction is also important in the development of pediatric asthma. Research done in rural and urban parts of China on 854 children revealed that physician diagnosed asthma was significantly lower in children living in rural areas. Personal and family history of atopy, high consumption of milk products, and hospitalization younger than three years of age were significantly associated with asthma. Similarly, being a member of a crop-farming family and dust endoxtoxin levels were negatively associated with asthma in the child. 16 Lautenbacher et al 17 investigated the effects of vitamin D on pulmonary function and compared obese and non-obese asthmatic children. Although the frequency of vitamin D deficiency was not different between groups, FEV1 and FRC were significantly worse in vitamin D deficient obese children than in normal-weight children. Moreover, TNF and IL-8 were higher in obese asthmatics, while the Th2 cytokine IL13 was higher in normal-weight asthmatics. However, these inflammatory measures were not related to the association of vitamin D deficiency with poor lung function; thus implying an independent effect of vitamin D deficiency. Coexistence of obesity and poor asthma control is well known, but body mass index (BMI) may not reflect regional differences in adiposity. As part of the AsthMaP-2 Project that is an observational study of pediatric asthma, association of neck circumference and asthma control was assessed. 18 It was demonstrated that, in boys, neck circumference combined with BMI explained the variability of asthma control test better than BMI alone. Air pollution has a significant influence on respiratory health. Rice et al 19 Although inflammatory markers did not correlate with AHR, the degree of AHR was less in those study subjects who were receiving hyroxyurea. Their results demonstrate that there is a high prevalence of AHR in SCD patients and hydroxyurea may be helpful in decreasing AHR in SCD. Lunt et al 38 Impulse oscillometry (IOS) uses the forced oscillation technique to assess airway function and does not require the maximal forced expiratory maneuver needed for spirometry. 39 IOS measures total respiratory impedance (Z) which is a complex number that incorporates both the in and out phase elements of resistance; the former is resistance (R), and the latter is termed the reactance (X). R reflects the airway resistive properties of the respiratory system, while X reflects the visco-elastic and inertive elements of the respiratory system. Potential limitations of this method include a limit on the size of the patients studied due to limitations on the volume of the washout collection bag and an inability of detect leak since there is no PNT. This system will require further study in human subjects before determining its utility in clinical research and patient care. Tidal breathing analysis is a method to assess respiratory function that does not require sedation or manipulation of the infant's respiratory system. 45 Respiratory inductance plethysmography has been used to obtain tidal breathing data, but it only measures chest and abdominal excursion at two points, which does not accurately reflect the true mechanics of the respiratory system. Reinaux et al 46 used opto-electronic plethysmography (OEP) to measure motion at 52 sites placed in the thorax and abdomen of healthy infants and compared the results obtained using this system to those obtained using a mask with PNT. They found that measurement of tidal volume using OEP was in good agreement with that obtained using a PNT with a mean difference of only 0.02 mL. The ability to obtain tidal breathing measurements may lead to new insights into changes in chest and abdominal motion in pediatric respiratory disease. Bronchopulmonary dysplasia (BPD) is the most common respiratory complication of preterm birth. Despite advances in neonatal medicine, BPD still occurs in 30-50% of infants born before a gestational age (GA) of 29 weeks. 47 Acute viral bronchiolitis, due to RSV and other pathogens, continues to have a major impact worldwide on childhood mortality and hospital admissions, 51 is associated with subsequent asthma and allergy risk, 52 and could be increasing in incidence. 53 Cangiano et al 54 noted a higher incidence of acute bronchiolitis every 4 years among previously health term infants, largely due to RSV; rhinovirus was a less common cause and had less tendency to occur in seasonal clusters than RSV. While a commonly used standard definition for bronchiolitis is initial episode of wheezing in a child <12 months old, variability in how clinicians actually define bronchiolitis was highlighted in a report from Fernandes et al. 55 Beamer et al 56 Treatment for acute bronchiolitis remains largely supportive and progress has been made in reducing widespread use of corticosteroids and bronchodilators, which have previously been shown to be ineffective. 57 Flores et al 58 conducted a randomized clinical trial comparing 3% hypertonic saline to normal saline in previously healthy infants hospitalized with mild-to-moderate acute viral bronchiolitis. The median length of hospital stay, severity score, and need for supplemental oxygen did not differ significantly between groups. Patients receiving hypertonic saline had significantly more cough (46% vs 20%, P = 0.025). Thus, the study does not support the use of nebulized hypertonic saline over normal saline in therapy of hospitalized children with mild-to-moderate acute viral bronchiolitis. In another study with practical implications, Heikkila et al 59 Factors influencing delivered mean airway pressure during nasal CPAP with the RAM cannula Diagnostic accuracy of capnography during high-frequency ventilation in neonatal intensive care units The effect of prolonged lateral positioning during routine care on regional lung volume changes in preterm infants Role of electrical impedance tomography in clinical practice in pediatric respiratory medicine FGR in the setting of preterm sterile intra-uterine milieu is associated with a decrease in RDS Association of BNP, NTproBNP, and early postnatal pulmonary hypertension in very preterm infants Bronchopulmonary dysplasia impairs L-type amino acid transporter-1 expression in human and baboon lung Pulmonary ventilation and micro-structural findings in congenital diaphragmatic hernia Neonatal hyperoxia increases airway reactivity and inflammation in adult mice Perinatal nicotine exposure induces myogenic differentiation, but not epithelial-mesenchymal transition in rat offspring lung Perinatal nicotine exposure induces asthma in second generation offspring Respiratory effects of air pollution on children Respiratory function and symptoms in young preterm children in the contemporary era Four-locus gene interaction between IL13, IL4, FCER1B, and ADRB2 for asthma in Chinese Han children DNA methylation in newborns and maternal smoking in pregnancy: genome-wide consortium metaanalysis Associations of early life exposures and environmental factors with asthma among children in rural and urban areas of Guangdong Vitamin D and pulmonary function in obese asthmatic children Sex differences in the association between neck circumference and asthma Lifetime exposure to ambient pollution and lung function in children Association between trafficrelated air pollution and asthma in preschool children in a national Japanese nested case-control study Postpartum depression, a direct and mediating risk factor for preschool wheeze in girls Prenatal maternal stress and atopic diseases in the child: a systematic review of observational human studies Looking beyond patients: can parents' quality of life predict asthma control in children? Asthma action plan receipt among children with asthma 2-17 years of age Can a single dose response predict the effect of montelukast on exerciseinduced bronchoconstriction? Albuterol via metered-dose inhaler in children: lower doses are effective, and higher doses are safe Exhaled breath temperature measurement and asthma control in children prescribed inhaled corticosteroids: a cross sectional study Infection and inflammation in induced sputum from preschool children with chronic airways diseases Association between exhaled inflammatory markers and asthma control in children Concordance between bronchial hyperresponsiveness, fractional exhaled nitric oxide, and asthma control in children Patterns of growth and decline in lung function in persistent childhood asthma Differences in pulmonary functions in various racial groups Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations Pulmonary diffusing capacity in healthy African-American and Caucasian children Spirometric reference values for Hopi Native American children ages 4-13 years Pulmonary complications of sickle cell disease Airway hyperreactivity is frequent in non-asthmatic children with sickle cell disease Longitudinal assessment of lung function in children with sickle cell disease Clinical application of forced oscillation Respiratory impedance in patients with Duchenne muscular dystrophy Evaluation of children with cystic fibrosis by impulse oscillometry when stable and at exacerbation Respiratory impedance in children with cystic fibrosis using forced oscillations in clinic Changes in lung function measured by spirometry and the forced oscillation technique in cystic fibrosis patients undergoing treatment for respiratory tract exacerbation Accurate lung volume measurements in vitro using a novel inert gas washout method suitable for infants Tidal breathing analysis Tidal volume measurements in infants: opto-electronic plethysmography versus pneumotachograph Prematurity and respiratory outcomes program. comparisons and limitations of current definitions of bronchopulmonary dysplasia for the prematurity and respiratory outcomes program Lung function gain in preterm infants with and without bronchopulmonary dysplasia Mid-childhood lung function in a cohort of children with "new bronchopulmonary dysplasia Global and national burden of diseases and injuries among children and adolescents between 1990 and 2013: findings from the Global Burden of Disease Viral bronchiolitis in children Predictors of asthma following severe respiratory syncytial virus (RSV) bronchiolitis in early childhood Admission to hospital for bronchiolitis in England: trends over five decades, geographical variation and association with perinatal characteristics and subsequent asthma Bronchiolitis: analysis of 10 consecutive epidemic seasons Acute viral bronchiolitis: physician perspectives on definition and clinically important outcomes Spatial clusters of child lower respiratory illnesses associated with community-level risk factors Value in inpatient pediatrics network quality collaborative for improving hospital compliance with AAP bronchiolitis guideline (BQIP). A multicenter collaborative to reduce unnecessary care in inpatient bronchiolitis A randomized trial of nebulized 3% hypertonic saline with salbutamol in the treatment of acute bronchiolitis in hospitalized infants High-flow oxygen therapy is more costeffective for bronchiolitis than standard treatment-a decision-tree analysis Respiratory viral detection in children and adults: comparing asymptomatic controls and patients with community-acquired pneumonia Beta-lactam versus betalactam/macrolide therapy in pediatric outpatient pneumonia Paradoxical tuberculosisassociated immune reconstitution inflammatory syndrome in children Protracted bacterial bronchitis: the last decade and the road ahead Pediatric bronchiectasis: no longer an orphan disease Coccidioidomycosis in infants: a retrospective case series Interaction between 25-hydroxyvitamin D and variants at 17q12-21 on respiratory infections How to cite this article Pediatric pulmonology year in review 2016: Part 2