To assess within a feasibility study the correlation, agreement, and trending of continuous integrated distal capnography (dCap) with PaCO₂ in infants on HFV.

Sixteen premature infants [median (range) gestational age: 26.5 (24.7–34.7) weeks], ventilated with HFV (mean ± SD airway pressure: 8.1 ± 2.1 cmH₂O, FiO₂: 0.39 ± 0.21) for RDS, intubated with a double-lumen endotracheal-tube and whose data were recorded on a bedside computer participated in the study. Side-stream dCap was measured via the extra-port of a double-lumen endotracheal-tube by a Microstream capnograph, with a specially designed software for HFV and compared with simultaneous PaCO₂. Integrated time-window analysis of the data was performed retrospectively on data collected prospectively.

Analysis included 195 measurements. The correlation of dCap with PaCO₂ (r = 0.68, P < 0.0001) and the agreement (bias ± precision: −2.0 ± 10.7 mmHg) were adequate. Area under the ROC curves for dCap to detect high (>60 mmHg) or low (<35 mmHg) PaCO₂ was 0.79 (CI: 0.70–0.89) and 0.87 (CI: 0.73–1.00), respectively; P < 0.0001. Changes in dCap and in PaCO₂ for consecutive measurements within each patient were adequately correlated (r = 0.65, P < 0.0001).

Continuous integrated dCap is feasible in premature infants ventilated with HFV and can be helpful for trends and alarm for unsafe levels of PaCO₂. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.

Fungal pneumonia is a serious complication in immunocompromised children. It is difficult to diagnose because of the low sensitivity of clinical and standard laboratory tests. The aim of this study was to investigate the diagnostic impact of polymerase chain reaction (PCR) assays for fungal pathogens in bronchoalveolar lavage (BAL) fluid.

BAL samples obtained from hospitalized immunocompromised patients with clinical pneumonia between January 2007 and June 2009 were processed for microscopy and cultures in addition to PCR-based fungal assays. The results were compared between the standard and PCR methods.

Seventy-seven children with 100 episodes of pneumonia were included in the study. Fungal pathogens were detected by standard microbiological investigations in 10 episodes (10%) and by PCR-based assays alone in 20 episodes (20%). There was no significant difference in clinical improvement or mortality rate between patients diagnosed by the different methods. In 61 episodes, no fungal pathogen was identified by either method. Prolonged antifungal therapy was avoided in 43 episodes.

PCR-based assay for the diagnosis of fungal pulmonary infections may be a useful adjunct to clinical and standard microbiological techniques. The use of PCR may decrease the time to diagnosis, increase the rate of detection of fungal pathogens, and spare patients unnecessary antifungal treatment. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.

The earliest change associated with airflow obstruction in small airways is reflected in a concave shape on the maximum expiratory flow-volume loop (MEFVL). The shape of the MEFL changes with age but reference values for curvilinearity indices (CI) for preschool children have not been published. We aimed to describe the normal curvilinearity of healthy preschool MEFVL by CI (the β angle and the ratio of maximum expiratory flow when 50% of forced vital capacity remains to be expired/peak expiratory flow (MEF_50%/PEF)) and to test their capacity in detecting concavity in preschool children with wheezing disorders.

Spirometric data were obtained from 132 healthy preschool children and 171 3-to-5-year-old preschool children with wheezing disorders and reference values for CI calculated.

Mean (SD) β angle of healthy children was 203° (16°) and mean MEF_50%/PEF of healthy children was 0.71 (0.12) indicating convexity of MEFVL, both decreased with increasing age (P = 10⁻⁴). Children with wheezing disorders had lower z-score values of CI (P ≤ 10⁻⁶) indicating more concave MEFVL. Among the two CI, MEF_50%/PEF allowed for the best discrimination between healthy children and children with wheezing disorders (Wilks' lambda = 0.898, P = 10⁻⁷).

These CI can detect and quantify the concavity of the descending limb of the MEFVL in preschool children with wheezing disorders, MEF_50%/PEF having the highest sensitivity in detecting the concavity. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.

Many adolescents have poor asthma control and are at high risk for psychosocial problems. However, structured assessment of asthma control or psychosocial problems is still not implemented in routine asthma care. Pediatricians typically rely on their clinical view and physiological measurements. To date, it is unknown whether clinical and patient reported outcomes are interrelated. Furthermore, there is no consensus on who should be the informant; the adolescent or his caregiver.

This study aimed to assess the relationship between patient and caregiver reported outcomes [Asthma Control Questionnaire and Strengths and Difficulties Questionnaire (SDQ)] and physiological parameters (FEV1 and Fractional exhaled Nitric Oxide) in adolescents (aged 11–16) with asthma.

A multicenter observational study was performed in four Dutch pediatric outpatient departments. Association between asthma control, physiological parameters, and results of psychosocial questionnaires completed by both adolescent and caregiver was analyzed.

Forty-eight adolescents and their caregivers participated in this study. Asthma was uncontrolled in about 30%. Asthma control was not associated with age, gender, FEV1, FeNO, or psychosocial problems. Agreement between adolescents and caregivers about how well asthma was controlled was moderate (κ = 0.577, P < 0.01).

Asthma control, physiological parameters, and psychosocial problems are different domains of health status. It could be suggested to use validated patient and caregiver reported outcomes in routine adolescent asthma care.

Patient and caregiver reported outcomes on asthma control and the presence of psychosocial problems add valuable, unique information to physiological parameters in adolescent asthma management. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.

(1) To examine whether infants with severe bronchiolitis, fulfilling criteria for further respiratory support, could be managed outside a Pediatric Intensive Care Unit (PICU) with non-invasive ventilation (NIV) alone. (2) To study the characteristics, clinical course and outcome of NIV responders and non responders to assess safety and efficacy and inform guideline construction.

Infants with severe bronchiolitis can be safely managed with NIV outside a PICU.

Retrospective case review.

Cohort of infants with objective evidence of severe bronchiolitis requiring respiratory support nursed in a Pediatric High Dependency Unit (PHDU) and/or Intensive Care Unit (ICU) between 2001 and 2007.

Analysis of patient characteristics and respiratory parameters at admission and initiation of ventilation, changes after 2 and 4 hr of NIV or invasive ventilation, complications, short and long-term outcomes were analyzed.

One thousand and thirty-five infants with bronchiolitis were admitted with 67 ventilation episodes identified from 65 patients. Fifty-five episodes, including 34 with apnea, were treated exclusively with NIV. Six infants failed to respond and were invasively ventilated. Six patients were invasively ventilated at presentation. Non-responders had a significantly higher rate of bacterial infection. Significant improvements in respiratory parameters in responders occurred by 2 hr and sustained at 4 hr. Duration of hospital stay, ventilation requirement and oxygen requirement were significantly shorter in responders. Short and longer-term follow up data did not identify any adverse effects related to NIV.

NIV was effective in 80% of infants receiving respiratory support for severe bronchiolitis. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.

Gastroesophageal reflux (GER) is common in children with airway disorders. Previous studies have shown an association between upper airway obstruction and GER in experimental animal models. However, the cause and effect relationship between intrathoracic airway obstruction (IAO) and GER is obscure. The goal of this study is to investigate the association between IAO and GER using the canine model.

In sedated dogs, a telemetric implant was placed subcutaneously (with one pressure sensor tip each in intrapleural space and abdomen) to monitor intrapleural pressure (IPP) and intrabdominal pressure (IAP). The IPP and the IAP were monitored intraoperatively and in conscious dogs on the 7th to 10th postoperative days. GER was assessed by determining the reflux index (RI), based on the intraesophageal pH recording performed continuously for a 24 hr period using a pH probe. After 2–3 weeks following placement of the telemetric implant, IAO was surgically created in the dog. After maintaining IAO for 2 weeks, the IPP, IAP, and pH measurements were monitored again following the same protocol as before IAO.

After the creation of IAO, there was no significant change observed in the mean RI either in the distal (P = 0.716) or proximal (P = 0.962) esophageal lumens. The IPP became significantly more negative (P = 0.006) and the IAP turned significantly negative (P < 0.001) from being positive compared to the respective values before IAO. However, transdiaphragmatic pressure (Pdi) did not change significantly (P = 0.08).

We conclude that moderate IAO does not cause GER in our animal model. It can be explained by the absence of significant change in Pdi after creation of IAO. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.

Little is known about molecular changes in lungs of fetal rabbits with surgically induced diaphragmatic hernia (DH). Therefore, we examined in this model gene expressions of pivotal molecules for the developing lung.

At day 23 of gestation, DH was created in 12 fetuses from 4 does. Both lungs from six live DH fetuses and from six unoperated controls were harvested and weighed at term. Transcription of 15 genes involved in alveolarization, angiogenesis, regulation of vascular tone, or epithelial maturation was investigated by real-time quantitative polymerase chain reaction.

DH decreased lung-to-body weight ratio (P < 0.001). A bilateral downregulation was seen for genes encoding for tropoelastin (P < 0.01), lysyl oxidase (P < 0.05), fibulin 5 (P < 0.05), and cGMP specific phosphodiesterase 5 (P < 0.05). Lower mRNA levels for endothelial nitric oxide synthase occurred in the ipsilateral lung (P < 0.05).

Experimental DH in fetal rabbits disrupted transcription of genes implicated in lung growth and function. Similarities with the human disease make this model appropriate for investigation of new prenatal therapies. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.

Pulmonary dysfunction represents one of the most undervalued and less recognized complications in patients with β-thalassaemia.

The aim of this study was to assess the pattern of pulmonary dysfunction and consequently to investigate possible associated factors that might contribute to lung impairment in young patients with β-thalassaemia major.

Fifty-two children and young adults (mean age: 21.33 ± 6.24 years) with β-thalassaemia major on conventional treatment (transfusions and iron chelation therapy) were included in the study. A complete computerized pulmonary function testing (PFT) system for recording pulmonary diffusion capacity and simultaneous determination of alveolar volume and pulmonary volumes was equipped.

Results showed that 20 patients (38.46%) had restrictive pulmonary pattern that was preferentially observed in older and shorter patients. Serum ferritin levels were higher in the restrictive group (2,096 ± 1,831 ng/dl) compared to patients with normal pulmonary function (1,354 ± 942 ng/dl) (P = 0.066). Diffusional impairment characterized by significantly lower DLCO*% values, was observed in the restrictive group (P = 0.004), implicating the 62.5% of the population studied. Paired linear correlations showed that age was negatively correlated to DLCO*% (r = −0.548, P < 0.001) and SaO₂% (r = −0.789, P < 0.001) and with most of the pulmonary functional parameters that determine a restrictive. Multivariate regression analysis identified age as the major predictor for restrictive pulmonopathy followed by serum ferritin levels.

Our study shows that pulmonary impairment is shown in a great proportion even among asymptomatic young thalassaemic patients, thus, regular screening of pulmonary function should be adopted in the routine clinical follow up of these patients. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.

Non-invasive high frequency high frequency oscillatory ventilation through nasal prongs (nHFOV) has been proposed to combine the advantages of oscillatory pressure waveform and non-invasive interface. We studied the effect of oscillation amplitude and inspiratory time on the pressure transmission and tidal volume delivery through different nasal prongs.

In vitro mechanical study on a previously described bench model of nHFOV. The model was built connecting SM3100A tubings to a neonatal lung model, via two differently sized binasal prongs. A circuit with no nasal prongs was used as control. Tidal volume (T_v), oscillatory pressure ratio (ΔP_dist/ΔP_prox), and ventilation (DCO₂) were measured across a range of amplitudes and inspiratory times (I_T). Measurements were performed with a low-dead space hot wire anemometer coupled with a pressure transducer.

Using both nasal prongs, T_v, ΔP_dist/ΔP_prox, and DCO₂ were 83%, 40%, and 71%, respectively, of those provided with the control circuit. No differences were noticed between small and large prongs. T_v and ΔP_prox were linked by a quadratic relationship. T_v plateaus for amplitude values >65 cmH₂O. ΔP_dist/ΔP_prox shows same tendency. Same results were obtained with both types of prongs and with increasing I_T. On the whole, mean T_v was higher with I_T at 50% than at 33% (2.4 ml vs. 1.4 ml; P < 0.001).

Changing oscillation amplitude and I_T has a significant effect on ventilation. Varying these two parameters provides a theoretical T_v within the ideal values for HFOV also using the smallest nasal prongs. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.

There are several adult studies using computed tomography (CT-scan) to examine lung aeration changes during or after a recruitment maneuver (RM) in ventilated patients with acute lung injury (ALI). However, there are no published data on the lung aeration changes during or after a RM in ventilated pediatric patients with ALI.

To describe CT-scan lung aeration changes and gas exchange after lung recruitment in pediatric ALI and assess the safety of transporting patients in the acute phase of ALI to the CT-scanner.

We present a case series completed in a subset of six patients enrolled in our previously published study of efficacy and safety of lung recruitment in pediatric patients with ALI. Intervention: RM using incremental positive end-expiratory pressure.

There was a variable increase in aerated and poorly aerated lung after the RM ranging from 3% to 72% (median 20%; interquartile range 6, 47; P = 0.03). All patients had improvement in the ratio of partial pressure of arterial oxygen over fraction of inspired oxygen (PaO₂/FiO₂) after the RM (median 14%; interquartile range: 8, 72; P = 0.03). There was a decrease in the partial pressure of arterial carbon dioxide (PaCO₂) in four of six subjects after the RM (median −5%; interquartile range: −9, 2; P = 0.5). One subject had transient hypercapnia (41% increase in PaCO₂) during the RM and this correlated with the smallest increase (3%) in aerated and poorly aerated lung. All patients tolerated the RM without hemodynamic compromise, barotrauma, hypoxemia, or dysrhythmias.

Lung recruitment results in improved lung aeration as detected by lung tomography. This is accompanied by improvements in oxygenation and ventilation. However, the clinical significance of these findings is uncertain. Transporting patients in early ALI to the CT-scanner seems safe and feasible. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.

In 2005 the Cystic Fibrosis (CF) Foundation recommended that children with CF maintain a body mass index (BMI) ≥50th percentile. Our study evaluated if gastrostomy (GT) placement increases the likelihood of reaching that goal compared to a standardized nutrition protocol.

Retrospective study of 20 children with CF ages 2–20 years with GTs placed from 2005 to 2010. Each case was pair-matched on age, sex, pancreatic status, BMI, and lung function with a nonGT child with CF. Outcome measures included nutritional status and lung function at 6 months and 1 year.

At baseline, mean ± SD BMI Z-scores were similar (cases −1.19 ± 0.60, controls −1.10 ± 0.50; P = 0.10). Cases had a significant 6-month increase in mean BMI Z-score to −0.29 ± 0.84 compared to −1.02 ± 0.67 for controls (P < 0.001). By 1 year, the change in mean BMI Z-score was less different (cases −0.41 ± 0.76, controls −0.71 ± 0.51; P = 0.07). Both groups had stable lung function. From exact logistic regression analysis, the odds ratio for cases compared to controls of reaching BMI ≥50th percentile was 9.70 (95% CI: 1.05–484.7; P = 0.04) at 6 months and 3.65 (95%CI: 0.69–25.86; P = 0.16) at 1 year.

Our study suggests that children with CF who receive GTs are more likely to achieve BMI ≥50th percentile than matched children without GTs. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.

Prenatal maternal smoking and prematurity independently affect wheezing and asthma in childhood.

We sought to evaluate the interactive effects of maternal smoking and prematurity upon the development of early childhood wheezing.

We evaluated 1,448 children with smoke exposure data from a prospective urban birth cohort in Boston. Maternal antenatal and postnatal exposure was determined from standardized questionnaires. Gestational age was assessed by the first day of the last menstrual period and early prenatal ultrasound (preterm < 37 weeks gestation). Wheezing episodes were determined from medical record extraction of well and ill/unscheduled visits. The primary outcome was recurrent wheezing, defined as ≥ 4 episodes of physician documented wheezing. Logistic regression models and zero inflated negative binomial regression (for number of episodes of wheeze) assessed the independent and joint association of prematurity and maternal antenatal smoking on recurrent wheeze, controlling for relevant covariates.

In the cohort, 90 (6%) children had recurrent wheezing, 147 (10%) were exposed to in utero maternal smoke and 419 (29%) were premature. Prematurity (odds ratio [OR] 2.0; 95% confidence interval [CI], 1.3–3.1) was associated with an increased risk of recurrent wheezing, but in utero maternal smoking was not (OR 1.1, 95% CI 0.5–2.4). Jointly, maternal smoke exposure and prematurity caused an increased risk of recurrent wheezing (OR 3.8, 95% CI 1.8–8.0). There was an interaction between prematurity and maternal smoking upon episodes of wheezing (P = 0.049).

We demonstrated an interaction between maternal smoking during pregnancy and prematurity on childhood wheezing in this urban, multiethnic birth cohort. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.

High-frequency jet ventilation (HFJV) is often used to treat infants with pathologies associated with gas trapping and abnormal lung mechanics, who are sensitive to the adverse effects of suction.

This study aimed to investigate the effect of closed suction (CS), catheter size, and the use of active post-suction sighs on tracheal pressure (P_trach), and global and regional end-expiratory lung volume (EELV) during HFJV.

Six anaesthetized and muscle-relaxed adult rabbits were stabilized on HFJV. CS was performed using all permutations of three CS methods (Continual negative pressure, negative pressure applied during Withdrawal, and HFJV in Standby) and 6 French gauge (6FG) and 8 French gauge (8FG) catheter, randomly assigned. The sequence was repeated using post-suction sighs. P_trach, absolute (respiratory inductive plethysmography) and regional (electrical impedance tomography; expressed as percentage of vital capacity for the defined region of interest, %Z_VCroi) EELV were measured before, during and 60 sec post-suction.

CS methods exerted no difference on ΔP_trach, ΔEELV_RIP, or Δ%Z_VCroi. 8FG catheter resulted in a mean (95%CI) 20.0 (17.9,22.2) cm H₂O greater loss of P_trach during suction compared to 6FG (Bonferroni post-test). Mean (±SD) ΔEELV_RIP was −6(±3) and −2(±1) ml/kg with the 8 and 6FG catheters (P < 0.0001; Bonferroni post-test). ΔEELV was 31.7 (21.1,42.4) %Z_VCroi and 24.8 (10.9,38.7) %Z_VCroi greater in the ventral and dorsal hemithoraces using the 8FG. Only after 8FG CS was post-suction recruitment required to restore EELV.

In this animal model receiving HFJV, ΔP_trach, ΔEELV, and need for post-suction recruitment during CS were most influenced by catheter size. Volume changes within the lung were uniform. Pediatr Pulmonol. © 2012 Wiley Periodicals, Inc.

Rapid and reliable confirmatory sweat testing following a positive newborn screen (NBS) for cystic fibrosis (CF) is preferred to allow for early diagnosis and to decrease parental anxiety. The Cystic Fibrosis Foundation (CFF) recently recommended a quantity not sufficient (QNS) rate of ≤10% in infants <3 months of age referred for quantitative sweat chloride analysis. Two CFF-approved methods are available by which to quantitatively measure chloride concentration in sweat. Our objective was to compare the performance of the Macroduct® sweat collection system (MSCS) with the Gibson and Cooke technique (GCT) in the acquisition of samples for the determination of sweat chloride concentration in infants with a positive Minnesota State NBS for CF.

A retrospective database review of infants referred to the core Minnesota CF Center or its affiliate site for confirmatory sweat testing was performed to compare the QNS rates for the two techniques. Associations between birthweight, age at test, race, and QNS rates were examined.

Five hundred sixty-eight infants were referred for 616 sweat tests from March 2006 to January 2010. The mean age was 32.8 days at the initial sweat test. The GCT had a significantly higher QNS rate compared to the MSCS (15.4% vs. 2.1%, P < 0.0001). There was no association between age and the probability of QNS. The probability of QNS decreased as birthweight increased (P = 0.02). After adjusting for age, the odds of QNS using the GCT remained 8.34 (95% CI: 3.72–18.71) times that of the MSCS. Non-White infants had a significantly higher likelihood of QNS compared to non-Hispanic White infants (P = 0.0025).

Given the performance of the MSCS, the Minnesota CF Center has implemented the MSCS as its method of choice for diagnostic sweat testing in infants following a positive state NBS. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

To examine cystic fibrosis (CF) physician adherence to the 2007 CF Foundation (CFF) Pulmonary Guidelines for Chronic Medications. Specifically adherence and barriers to prescribing level A medication recommendations (i.e., inhaled tobramycin and dornase alfa) and level B medication recommendations (i.e., macrolide antibiotics and hypertonic saline) were studied.

During Spring 2010, the CFF emailed survey invitations to directors of 136 accredited CF care centers treating 50+ CF patients. Directors were asked to forward the invitations to their physician colleagues. One hundred thirty-three surveys were included in the analyses, representing 92 centers. Barriers were conceptualized based on Cabana et al.'s framework for adherence to guidelines. Adherence was assessed via a case vignette.

Logistic regression analysis revealed that higher outcome expectancy (OR = 1.099, CI 1.010–1.196) and fewer environmental/system barriers (OR = 1.484, CI 1.158–1.902) were significantly associated with Vignette Adherence. A trend for an association between Familiarity and Vignette Adherence (OR = 1.642, CI 0.953–2.828) was evident, while no demographic variables were significantly associated with Vignette Adherence.

Targeting outcome expectancy and external barriers with multifaceted, ongoing interventions may improve guideline adherence. Pulmonologists are clearly looking for empirical evidence that these medications benefit their patients over the long-term and offset patient treatment burden with improved health. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

Chest CT scans detect structural abnormalities in children with cystic fibrosis (CF), even when pulmonary function tests (PFTs) are normal. The use of chest CT is limited in clinical practice, because of concerns over expense, increased resource utilization, and radiation exposure. Quantitative chest radiography scores are useful in detecting mild lung disease, but whether they are sensitive to the presence of CT scan abnormalities has not been evaluated.

To determine in a cross-sectional study if quantitative chest radiography is a more sensitive marker of chest CT abnormalities than other lung disease surrogates.

Brody chest CT scores were calculated for 81 children enrolled in the Wisconsin CF Neonatal Screening Project. We determined the sensitivity for Wisconsin (WCXR) and Brasfield (BCXR) chest radiography scores, PFTs, positive cultures for P. aeruginosa (PA), and parental report of symptoms to detect a Brody score worse than the median score for study participants.

The mean FEV₁ for the study population was 91% predicted. Abnormal WCXR and BCXR scores had the highest sensitivity to detect a chest CT score worse than the median; abnormal PFTs, parental report of symptoms, and the presence of PA had much lower sensitivity (P < 0.001).

In this cross sectional study, quantitative chest radiography has excellent sensitivity to detect an abnormal chest CT and may have a role in monitoring lung disease progression in children with CF. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

To describe a series of ex-preterm infants admitted to pediatric intensive care unit due to impending hypoxaemic respiratory failure complicated by pulmonary hypertension (PH) who were treated electively combining noninvasive ventilation (NIV) and nebulized iloprost (nebILO).

Open uncontrolled observational study.

Pediatric Intensive Care Unit, University Hospital.

Ten formerly preterm infants with impending hypoxaemic respiratory failure and PH, of whom eight had moderate to severe bronchopulmonary dysplasia.

Median age and body weight were 6.0 (2.75–9.50) months and 4.85 (3.32–7.07) kg, respectively. We observed a significant early oxygenation improvement in terms of PaO₂/FiO₂ increase (P = 0.001) and respiratory rate reduction (P = 0.01). Hemodynamic also improved, as shown by heart rate (P = 0.002) and pulmonary arterial pressure systolic/systolic systemic pressure (PAPs/SSP) ratio reduction (P = 0.0137). NebILO was successfully weaned in positive response cases: 4 infants were discharged on oral sildenafil. Three patients failed noninvasive modality and needed invasive mechanical ventilation; hypoxic–hypercarbic patients were most likely to fail noninvasive approach. Only one patient requiring invasive ventilation died and surviving babies had a satisfactory 1-month post-discharge follow-up.

The noninvasive approach combining NIV and nebILO for ex-preterm babies with impending respiratory failure and PH resulted to be feasible and quickly achieved significant oxygenation and hemodynamic improvements. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

Primary tracheobronchomalacia (TBM) is a disease of the large airways. Long-term follow-up studies of TBM patients have not been reported. This study was undertaken to further elicit the natural history of this condition and the presence of concomitant reactive airways disease through clinical profiling and pulmonary function testing.

Twenty-one children diagnosed with TBM by bronchoscopy between 1998 and 2001 in Queensland were recruited in 2008. Parents completed a questionnaire detailing their child's respiratory symptoms over the previous 12 months. Children then undertook pulmonary function and flow–volume loop classification. Mannitol bronchial provocation testing or post-bronchodilator spirometry was performed to assess for the confounding presence of reactive airways disease.

Data from 19 children (12 males) were able to be analyzed. The median age was 9.4 (range 7.6–14.3) years. 15 parents indicated their child's symptoms were unresolved. The mean FEV₁ was 81% predicted with 7 <80% predicted. This was significantly lower than the percent predicted population mean (P = 0.0005). Mean FEV₁/FVC, FEF_25–75, and PEF were also significantly reduced (P = < 0.0001). Four participants had a classical TBM flow–volume loop on analysis. One of 15 (6.7%) participants recorded a positive test for reactive airways disease.

Clinical symptom profiles and pulmonary function indicate persistent functional mechanical abnormalities of the large and small airways in TBM patients, and the absence of reactive airways disease. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

Both healthy preterm infants and those with bronchopulmonary dysplasia (BPD) have poor lung function during childhood and adolescence, although there is no evidence whether prematurity alone explains the reduction in lung function found in BPD infants. Our study seeks to know if lung function, measured in infancy by means of rapid thoracic compression with raised volume technique, is different between preterm infants with and without BPD.

Lung function was measured in 43 preterm infants with BPD and in 32 preterm infants without BPD at a chronological age range of 2–28 months. Forced vital capacity (FVC), forced expiratory volume at 0.5 sec, and forced expiratory flows at 50, 75, 85%, and 25–75% of FVC were obtained from maximal expiratory volume curves by means of rapid thoracic compression with raised volume technique. Maximal flow at functional residual capacity was measured using rapid thoracic compression at tidal volume. Multiple regression analysis and generalized least squares (GLS) random-effects regression model were used to control for variables such as gender, weeks of gestation, age, birth weight, and tobacco smoke exposure. A sub-analysis was performed in infants born at 28+ weeks of gestation.

BPD was associated to significantly lower flows (regression coefficients: −0.51, −0.54, −57, −0.53, and −0.82, respectively for FEF₅₀, FEF₇₅, FEF₈₅, FEF_25–75). This association was driven by males and maintained in the subgroup of infants born at 28+ weeks of gestation.

BPD is associated with an additional decrease of lung function during the first 2 years of life in infants born preterm. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

Smoking is the single most important risk factor for the development of chronic obstructive pulmonary disease, and more than 80% of adult smokers started smoking before the age of 20. The aim of our study was to evaluate the early impact of smoking on lung function, health, and well-being in adolescents.

Twenty-four non-smokers (10 male, 14 female, mean age 17.6 years) and 24 smokers (mean of 3.5 pack-years; 15 male, 9 female, mean age 17.8 years) were compared in terms of lung function, bronchial hyperreactivity (BHR), levels of exhaled carbon monoxide (eCO), exhaled nitric oxide (eNO), and blood counts. A questionnaire containing items from the ISAAC study was used to detect differences in health and well-being.

There were no significant differences in lung function values between non-smokers and smokers (VC 95% vs. 103%, FEV₁ 106% vs. 116%, FEV₁%/VC MAX 94.6% vs. 95.2%), whereas BHR significantly differed (P < 0.05). Furthermore, significant differences were found for eCO, eNO, Hb, leukocytes, and neutrophils. Health and well-being in terms of sleep and physical activity were significantly worse in smokers.

Our results suggest an early impact of smoking on health after as few as 3.5 pack-years. Early signs of smoking are an increase in BHR, changes in blood count and a decrease of eNO even before changes in lung function become apparent. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

Nonacid gastroesophageal reflux (GER), particularly in patients taking acid suppression, has been implicated as a cause of respiratory infections. We hypothesize that children with cystic fibrosis (CF) and a higher nonacid reflux burden have greater rates of Pseudomonas aeruginosa (Pa) infection than patients with a lower reflux burden.

We reviewed the multichannel intraluminal impedance (pH-MII) tracings of 35 patients with CF between 2003 and 2010. We compared the reflux profiles between those patients who were Pa positive and Pa negative.

The mean age was 13.5 ± 5.8 years. Twenty-seven patients (76%) were Pa positive. Ninety seven percent of patients were taking proton pump inhibitors during pH-MII testing. The mean percentage of time pH was <4 was 8.5 ± 12%. Pa patients had a significantly higher total, acid and proximal nonacid reflux burden (P < 0.009). There was a negative correlation between nonacid reflux burden and FEV1 (r = −0.397, P = 0.03) and between total number of reflux events and FEV1 (r = −0.474, P = 0.009). After adjusting for age and FEV1, total reflux burden remains significantly associated with Pa positivity (P = 0.055).

Increased reflux burden may predispose patients to Pa infection and worse lung function. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

To define reference ranges for oxygen saturation (SpO₂) values in healthy full-term infants in the first days of life and in preterm infants off supplemental oxygen as they approach neonatal intensive care unit (NICU) discharge.

From April 2009 to March 2010, we enrolled convenience samples of full-term infants from the newborn nursery and former preterm infants who did not require supplemental oxygen at the time of discharge from the NICU. Overnight SpO₂ and signal quality recordings were obtained and analyzed for duration of artifact-free recording time (AFRT), time (s) with SpO₂ less than several different target saturations (90–95%), and number of falls in SpO₂ by ≥4% and ≥10%.

We studied 102 full-term infants and 52 preterm infants. Preterm and full-term infants spent similar amounts of time less than 90%, 91%, 92%, 93%, 94%, and 95% although preterm infants had more falls in SpO₂ by ≥4% per hour of AFRT. Over 67% of term and preterm infants spent less than 6% of their time below 93%.

These data represent reference SpO₂ ranges for both preterm infants not requiring supplemental oxygen at NICU discharge and full-term infants in the first days of life. As we currently lack guidelines dictating the optimal target oxygen saturations for infants and the acceptable maximal time that they can safely spend below set target saturations, our data may serve as a guide to interpreting SpO₂ recordings of premature outpatient infants who are weaning from supplemental oxygen. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

We aimed to determine the correlation and the agreement between end-tidal carbon dioxide (ETCO₂) and partial pressure of arterial carbon dioxide (PaCO₂) in very low birth weight infants (VLBWI); furthermore, we assessed factors that could affect the ETCO₂–PaCO₂ relationship.

Simultaneous end-tidal and arterial CO₂ pairs were obtained from ventilated VLBWI who were monitored by mainstream capnography and had umbilical arterial catheter. Correlation and agreement between ETCO₂ and PaCO₂ were evaluated by using Spearman test and Bland-Altman method, respectively.

A total of 143 simultaneous ETCO₂–PaCO₂ pairs were analyzed from 45 ventilated VLBWI. There was a significant correlation (r = 0.69; P < 0.0001) between ETCO₂ and PaCO₂ values. The ETCO₂ value was lower than the corresponding PaCO₂ value in 94% pairs, with a mean bias of 13.5 ± 8.4 mmHg (95% agreement levels, −3.0 to 29.9 mmHg). Mean PaCO₂–ETCO₂ bias was similar between ELBWI (13.1 ± 7.7 mmHg; 95% agreement levels, −1.9 and 28.2 mmHg) and infants with birth weight 1,001–1,500 g (14.8 ± 9.7 mmHg; 95% agreement levels −4.3 and 33.8 mmHg). The bias between ETCO₂ and PaCO₂ was significantly increased with increasing FiO₂, mean airway pressure and oxygenation index. Within each patient, there was a positive correlation (r = 0.78, P < 0.0001) between the changes in PaCO₂ and the simultaneous changes in ETCO₂.

In ventilated VLBWI, the correlation between mainstream ETCO₂ and PaCO₂ is good, but the agreement is poor and negatively influenced by the severity of pulmonary disease. Capnography is feasible in ELBWI. ETCO₂ should not replace PaCO₂ measurements in ventilated VLBWI, but may have a role to detect trends of PaCO₂. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

To analyze cross-sectional and longitudinal associations between lung function measures and clinical features in a cohort of preschool children with cystic fibrosis (CF).

Longitudinal eight-center observational study of children with CF aged 36–60 months at enrollment, who underwent semiannual pulmonary function tests (PFTs) for up to 2 years consisting of spirometry (all 8 sites), forced oscillometry (FO, 5 sites), and measures of thoracoabdominal asynchrony using respiratory inductive plethysmography (IP, 5 sites).

Ninety-three subjects were enrolled; 181 acceptable spirometry measurements from 71 subjects, 128 FO from 47 subjects, and 142 IP from 50 subjects were available for analysis. Cross sectional analyses did not detect an association between any PFT parameter at enrollment and Pseudomonas aeruginosa (Pa) status, CF gene mutation class, Wisconsin cough score, Shwachman score, environmental tobacco smoke exposure, family history of asthma, or nutritional indices. In longitudinal analyses, Pa infection within 6 months preceding enrollment was associated with a significantly greater rate of decline in z-scores for forced expiratory flow between 25 and 75% of forced vital capacity (FEF_25–75) (−1.3 vs. −0.4 Z scores/year, P = 0.024) and greater thoracoabdominal asynchrony measured by IP (mean phase angle difference 4.6°, P = 0.004). No other significant longitudinal associations were observed.

Prior Pa infection is associated with a greater rate of decline in FEF_25–75 z-score and mild thoracoabdominal asynchrony in preschool children with CF. In this multicenter US study, significant associations between other lung function measures and clinical features were not detected. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

Conducting clinical trials in cystic fibrosis (CF) preschoolers has been limited by lack of sensitive lung function measures performed across sites.

(1) Assess feasibility and short-term reproducibility of spirometry, forced oscillometry (FO), and inductance plethysmography (IP) in a multi-center preschool population; (2) compare ability of each technique to differentiate lung function of CF preschoolers and controls; (3) evaluate longitudinal changes in lung function; (4) estimate sample sizes for future trials.

A longitudinal, multi-center study of CF preschoolers was conducted utilizing standardized equipment, rigorous site training, and centralized lung function data review. CF subjects participated in up to four study visits 6 months apart, plus a 2-week reproducibility visit. Controls had one study visit.

Ninety-three CF subjects and 87 controls participated. Acceptability rates were lowest for spirometry (55%) and highest for IP (77%). Spirometry success increased with age and having a prior acceptable measurement. FEV₁, FEV_0.5, and FEF_25–75 were lower for CF subjects than for controls; spirometric z-scores declined with age. IP measures of thoracoabdominal asynchrony were greater for CF subjects than for controls. FO indices did not distinguish CF from controls. FEV₁ and FEV_0.5 are able to detect the smallest treatment effect for a given sample size.

Spirometry appears more sensitive than IP or FO for detecting lung disease in CF preschoolers; spirometric indices decline with age. Future trials using spirometry should include a run-in period for training and require acceptable data prior to enrollment. However, near-normal spirometric measurements in CF preschoolers may lead to difficulty detecting a treatment effect. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

Topiramate, which is used as an anticonvulsant and for migraine prophylaxis in children, causes oligohydrosis as a side-effect, but its effect on sweat chloride concentrations has not been studied systematically.

Twenty-one children receiving topiramate and 20 healthy controls with no signs or symptoms of pulmonary or gastrointestinal disease and a negative family history for cystic fibrosis (CF) underwent bilateral pilocarpine iontophoresis and sweat collection via Macroduct® system.

Adequate samples (>15 µl volume) were obtained from 17/19 topiramate subjects (89%), and 19/20 (95%) controls. The mean sweat chloride concentration was 37.7 ± 18.8 mmol/L for patients receiving topiramate, and 15.9 ± 6.9 mmol/L for controls (p = 0.0001). The mean sweat volume was 29.1 ± 17.4 µl for patients receiving topiramate, and 41.2 ± 17.5 µl for controls (p = 0.037). Overall 8/17 (47%) of patients on topiramate with a measurable sweat chloride had either an intermediate (>40 mmol/L but <60 mmol/L) or elevated (>60 mmol/L) sweat chloride test result, while 0/19 control subjects had elevated sweat chloride (p = 0.0008). Further analysis of the in vitro activity of topiramate on cultured human bronchial epithelial cells in modified Ussing chambers showed no differences in chloride conductance measured in cells exposed to 10 or 50 µg/ml of topiramate when compared to non-exposed cells.

This is the first report of a medication affecting sweat chloride values and shows that topiramate therapy can cause elevated sweat chloride concentrations in the absence of clinical manifestations of CF. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

Multi-center research studies that include pulmonary function as an objective outcome are increasingly important in pediatric respiratory medicine. The need for local controls rather than depending on published normative data for lung function remains debatable.

To compare pulmonary function in childhood controls with no respiratory symptoms from three centers in the United Kingdom and ascertain the extent to which current reference equations are appropriate for this population.

Spirometry, plethysmographic lung volumes, and specific airways resistance (sRaw) were measured within specialized pediatric laboratories in children from three geographical locations throughout the UK (London, Leicester, and Glasgow), using identical equipment, software and standard operating procedures. Results were compared between centers and in relation to recent or commonly used UK pediatric reference values.

Pulmonary function was assessed in 94 healthy children (mean (SD) age: 7.7 (0.6) years; 88% white Caucasians; ∼30 from each center). There were no significant differences in background demographics or spirometric outcomes when compared between centers. By contrast, statistically significant differences in plethysmographic lung volumes and sRaw were observed between-centers. Significant differences in relation to published reference data for white subjects were noted for FEV₁ in all three centers and occasionally for other lung function measures but the differences from predicted values were small (within ± 0.5 z-score) and not clinically significant.

After appropriate inter-laboratory standardization, spirometric measurements in children can be measured in different centers without evidence of systematic differences. However, even after extensive standardization procedures, plethysmographic measures appear more prone to inter-center differences and cannot, at present, be reliably compared across centers without incorporating controls at each location. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

The use of portable fractional exhaled nitric oxide (FENO) devices is increasingly common in the diagnosis and management of allergic airways inflammation.

We tested two handheld FENO devices, to determine (a) if there was adequate intradevice repeatability to allow the use of single breath testing, and (b) if the devices could be used interchangeably. In a mixed pediatric population, including normal, asthmatic, and children with peanut allergies, 858 paired values were collected from the NIOX-MINO® and/or the NObreath® devices.

The NIOX-MINO® showed excellent repeatability (mean difference of 0.1 with 95% limits of agreement between −7.93 to 7.72 ppb), while the NObreath® showed good repeatability (mean difference of −1.61 with 95% limits of agreement between −14.1 and 10.8 ppb). Intradevice repeatability was good but not adequate and the NIOX-MINO® systematically produced higher results than the NObreath® [mean difference of 7.8 ppb with 95% limits of agreement from −11.55 to 27.52 ppb (−33% to 290%)].

Our results support the manufacturer's advice that single breath testing is appropriate for the NIOX-MINO®. NObreath® results indicate that the mean of more than one breath should be utilized. The devices cannot be used interchangeably. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

To establish children and adolescents' perspectives regarding their asthma and its impact upon their daily lives.

A 14-item questionnaire.

Canada, Greece, Hungary, The Netherlands, the United Kingdom, and South Africa.

Children/adolescents (aged 8–15 years) with physician-diagnosed asthma.

Interviews were conducted by telephone (Canada, Greece, Hungary, The Netherlands, and the United Kingdom) or face-to-face (South Africa).

Asthma symptoms, impact on activities, and quality of life.

Of the 943 children/adolescents interviewed, 60% were male. Most (81%) described their asthma as “not too bad” or “I only get it every now and then,” with only 4% reporting their asthma as being “very bad”; however, 92% experienced asthma-related coughing and 59% reported nocturnal awakening. Over half (57%) of children/adolescents believed they could predict when their asthma would make them ill; the most common initial symptoms being breathlessness (41%) and bad cough (33%). They considered the worst things about having asthma to be the symptoms of an asthma attack (32%) and not being able to play sport (25%). Almost half (47%) of children/adolescents felt that their asthma affected their ability to play sport or engage in physical activity. One in ten reported they had suffered asthma-related bullying.

Children/adolescents underestimate the severity of their asthma, and overestimate its control, indicating that they expect their illness to be symptomatic. Asthma has a substantial impact on their daily lives, particularly on physical activity and social functioning. Efforts are required to improve asthma control and expectations of health in children/adolescents. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

Parapneumonic effusion has been reported to develop either in typical bacterial infection or in viral pneumonia with bacterial co-infection and to cause death. Swine-origin influenza A (H1N1) virus infection can be accompanied with pleural effusion; however, there are no reports about the significance of pleural effusion in H1N1 pneumonia. We retrospectively analyzed both the clinical characteristics and the significance of pleural effusion associated with H1N1 pneumonia in children and adolescent.

Eighty-nine patients who were admitted with H1N1 pneumonia were divided into two groups: 17 patients with pleural effusion (i.e., the effusion group), and 72 patients without pleural effusion (the non-effusion group).

Lymphopenia (P = 0.030), elevation of the C-reactive protein (P = 0.026), and positive rate of anti-sptreptolysin O titer (P = 0.040) were significantly increased in the effusion group than in the non-effusion group. In addition, the need for treatment with both oxygen (P < 0.001) and oseltamivir (P = 0.013) was significantly increased in the effusion group. However, there was no significant difference between the two investigated groups in the duration of the treatment with intravenous antibiotics, the time of fever remission calculated from admission, and the days of hospital stay. Also, there was no documented bacterial co-infection in any of the studied groups.

This result suggested that pleural effusion in H1N1 pneumonia could develop without bacterial co-infection and had mild clinical course. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

Bronchiectasis is a well-known sequela of chronic pulmonary aspiration (CPA) that can result in significant respiratory morbidity and death. However, its true prevalence is unknown because diagnosis requires high resolution computed tomography which is not routinely utilized in this population. This study describes the prevalence, time course for development, and risk factors for bronchiectasis in children with CPA.

Using a cross-sectional design, medical records were reviewed for all patients with swallow study or airway endoscopy-confirmed aspiration in our airway center over a 21 month period. All patients underwent rigid and flexible bronchoscopy, and high resolution chest computed tomography. Prevalence, distribution, and risk factors for bronchiectasis were identified.

One hundred subjects age 6 months to 19 years were identified. Overall, 66% had bronchiectasis, including 51% of those less than 2 years old. The youngest was 8 months old. Severe neurological impairment (OR 9.45, P < 0.004) and history of gastroesophageal reflux (OR 3.36, P = 0.036) were identified as risk factors. Clinical history, exam, and other co-morbidities did not predict bronchiectasis. Sixteen subjects with bronchiectasis had repeat chest computed tomography with 44% demonstrating improvement or resolution.

Bronchiectasis is highly prevalent in children with CPA and its presence in young children demonstrates that it can develop rapidly. Early identification of bronchiectasis, along with interventions aimed at preventing further airway damage, may minimize morbidity and mortality in patients with CPA. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

Recent studies have shown the presence of lung disease in even asymptomatic infants with cystic fibrosis (CF). While pulmonary function testing (PFT) is often used to follow progression of lung disease and guide treatment in older children with CF, little data is available on change in infant PFTs in young children with CF.

To determine change in infant PFTs before and after antibiotic therapy for pulmonary exacerbation in infants with CF.

Retrospective cohort study of infants with CF who underwent clinically indicated infant PFTs before and after antibiotic therapy for CF pulmonary exacerbation at the University of North Carolina at Chapel Hill.

Pre- and post-antibiotics PFT data was available on 11 infants with CF, with a mean age of 102 weeks at time of first PFT. The majority of infants were symptomatic prior to antibiotics, and showed statistically significant improvement in clinical parameters following treatment. Prior to antibiotics, PFTs showed evidence of substantial obstructive disease (mean z-scores for FVC, FEV_0.5, and FEF_25-75 of −1.81, −3.06, and −4.5, respectively) and air-trapping/hyperinflation (mean z-scores for FRCpleth, RV, and RV/TLC of 8.86, 7.1, and 3.31, respectively). Following antibiotics, all of the above parameters showed statistically significant improvement.

We have shown a statistically significant improvement in infant PFT measures following antibiotic therapy in a cohort of 11 infants with CF, which paralleled improvement in clinical parameters. Though infant PFTs showed improvement, they remained abnormal in the majority of subjects, with persistent air-trapping and hyperinflation after antibiotic therapy. Our findings suggest that infant PFTs are sensitive to acute clinical changes in children with CF, and may be a useful tool in managing infants with CF. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

There are limited data assessing bronchodilator responsiveness (BDR) in infants and toddlers with recurrent wheezing, and factors associated with a positive response.

In a multicenter study of children ≤ 36 months old, we assessed the prevalence of and factors associated with BDR among infants/toddlers with recurrent episodes of wheezing.

Forced expiratory flows and volumes using the raised-volume rapid thoracic compression method were measured in 76 infants/toddlers [mean (SD) age 16.8 (7.6) months] with recurrent wheezing before and after administration of albuterol. Prior history of hospitalization or emergency department treatment for wheezing, use of inhaled or systemic corticosteroids, physician treatment of eczema, environmental tobacco smoke exposure, and family history of asthma or allergic rhinitis were ascertained.

Using the published upper limit of normal for post bronchodilator change (FEV_0.5 ≥ 13% and/or FEF_25–75 ≥ 24%) in healthy infants, 24% (n = 18) of children in our study exhibited BDR. The BDR response was not associated with any clinical factor other than body size. Dichotomizing subjects into responders (defined by published limits of normal) or by quartile to identify children with the greatest change from baseline (4th quartile vs. other) did not identify any other factor associated with BDR.

Approximately one quarter of infants/toddlers with recurrent wheezing exhibited BDR at their clinical baseline. However, BDR in wheezy infants/toddlers was not associated with established clinical asthma risk factors. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

Persistent lung atelectasis is difficult to treat and perfluorochemical (PFC) liquid may be an option for bronchioalveolar lavage (BAL).

A 4-year-old girl with spinal muscle atrophy was admitted in respiratory failure. On admission, the X-ray confirmed the persistence of total right-sided lung atelectasis, which had been present for 14 months. She was endotracheally intubated and ventilated from the day of admission. BAL with normal saline was performed twice without improvement. Following failed extubation and being dependent on continuous respiratory support, a trial of BAL using PFC liquid (Perfluorodecalin HP) was carried out. The PFC was delivered through the endotracheal tube on three consecutive days. A loading dose of 3 ml/kg was administered, followed by a varying dose in order to more effectively lavage the lungs. She tolerated the procedure well the first 2 days, although there were no clinical signs of improvement in the atelectasis. Intentionally, higher inflation pressures were applied after PFC instillation on day 3. Chest X-ray then showed hazy infiltrates on her left lung and she required more ventilatory support. However, lung infiltrates cleared over the next 3 days. A tracheotomy was done 6 days after the last PFC instillation. She had a slow recovery and was successfully decanulated. Clinical improvement of lung function was seen including less need of BiPAP and oxygen. A chest CT scan showed then functional lung tissue appearing in the previous total atelectatic right lung.

Lavage with PFC can safely be performed with a therapeutic effect in a child with unilateral total lung atelectasis. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

After intensive tobacco control efforts in recent decades, the prevalence of active smoking has decreased. However, the hazardous effect of indirect exposure to cigarette smoke is often underestimated, especially in children. We aimed to investigate the effect of parental smoking on the respiratory morbidity of the children of parents who smoke by evaluating the relationship between parental smoking behavior and children's respiratory symptoms.

We conducted a cross-sectional follow-up study of 31,584 children aged 6–11 in an urban community in Anyang City, Korea. The children's parents were asked about their smoking status and completed questionnaires regarding their children's symptoms related to asthma and other upper or lower respiratory illnesses. Our analysis focused on a comparison of the frequency of respiratory and ocular symptoms according to parental smoking status, whether it was non-smoking (Non-S), indirect passive smoking (third-hand smoking, THS) or direct passive smoking (second-hand smoking, SHS).

The children with Non-S patients were 40.9%, THS group 40.6%, and SHS group 18.5%. THS group showed lower ORs for most respiratory symptoms when compared with those of SHS group, however, THS group revealed increased ORs compared with Non-S in cough-related symptoms. There was a linear trend in frequencies of cough and sputum-related symptoms according to the degree of exposure to cigarette smoke (P < 0.05).

The prevalence of respiratory symptoms increased in children exposed to parental smoking including SHS and THS. To avoid the risk of respiratory and allergic disease by environmental tobacco smoke, absolute smoking cessation by parents is strongly recommended. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

A reliable standardized diagnosis of pneumonia in children has long been difficult to achieve. Clinical and radiological criteria have been developed by the World Health Organization (WHO), however, their generalizability to different populations is uncertain. We evaluated WHO defined chest radiograph (CXRs) confirmed alveolar pneumonia in the clinical context in Central Australian Aboriginal children, a high risk population, hospitalized with acute lower respiratory illness (ALRI).

CXRs in children (aged 1–60 months) hospitalized and treated with intravenous antibiotics for ALRI and enrolled in a randomized controlled trial (RCT) of Vitamin A/Zinc supplementation were matched with data collected during a population-based study of WHO-defined primary endpoint pneumonia (WHO-EPC). These CXRs were reread by a pediatric pulmonologist (PP) and classified as pneumonia-PP when alveolar changes were present. Sensitivities, specificities, positive and negative predictive values (PPV, NPV) for clinical presentations were compared between WHO-EPC and pneumonia-PP.

Of the 147 episodes of hospitalized ALRI, WHO-EPC was significantly less commonly diagnosed in 40 (27.2%) compared to pneumonia-PP (difference 20.4%, 95% CI 9.6–31.2, P < 0.001). Clinical signs on admission were poor predictors for both pneumonia-PP and WHO-EPC; the sensitivities of clinical signs ranged from a high of 45% for tachypnea to 5% for fever + tachypnea + chest-indrawing. The PPV range was 40–20%, respectively. Higher PPVs were observed against the pediatric pulmonologist's diagnosis compared to WHO-EPC.

WHO-EPC underestimates alveolar consolidation in a clinical context. Its use in clinical practice or in research designed to inform clinical management in this population should be avoided. Pediatr Pulmonol. © 2011 Wiley Periodicals, Inc.

Ventilator-dependent children have complex chronic conditions that put them at risk for acute illness and repeated hospitalizations.

To determine the 12-month incidence of and risk factors for non-elective readmission in children with chronic respiratory failure (CRF) after initiation on home mechanical ventilation (HMV) via tracheostomy.

A retrospective cohort study of 109 HMV patients initiated and followed at an university-affiliated children's hospital between 2003 and 2009. Patient characteristics are presented using descriptive statistics; generalized estimated equations are used to estimate adjusted odds ratios of select predictor variables for readmission.

The 12-month incidence of non-elective readmission was 40%. Close to half of these readmissions occurred within the first 3 months post-index discharge. Pneumonia and tracheitis were the most common reasons for readmission; 64% were pulmonary- or tracheostomy-related. Most demographic and clinical patient characteristics were not statistically associated with non-elective readmissions. Although, a change in the child's management within 7 days before discharge was associated readmissions shortly after index discharge.

Non-elective readmissions of newly initiated pediatric HMV patients were common and likely multifactorial. Many of these readmissions were airway-related, and some may have been potentially preventable. Pediatr Pulmonol. © 2011 Wiley-Liss, Inc.

Interferon-γ (IFN-γ) release assay (IGRA) is used for diagnosis of latent tuberculosis infection (LTBI), and for serial testing of active tuberculosis (TB). The aim of this study was to evaluate the results of IGRA for diagnosis and treatment monitoring of children with LTBI and children with TB. IGRA was performed in BCG vaccinated children before and six months after the beginning of treatment.

A total of 59 BCG vaccinated children aged 4–18 years were investigated due to exposure to active TB. The participants were divided into two groups: Group 1, children with LTBI (N = 41), and Group 2, children with TB (N = 18). IGRA (QuantiFERON-TB Gold In-Tube) was performed twice, i.e., before treatment and at the end of prophylaxis and therapy.

There was no significant difference in IFN-γ concentrations between Group 1 and Group 2 subjects either before or after the treatment. Difference between pre-treatment and post-treatment IFN-γ concentrations compared in either Group 1 or Group 2 was not statistically significant. During follow-up, children with LTBI did not develop active TB. In addition, in children with TB, signs and symptoms of TB improved with anti-TB therapy.

This study showed that the concentrations of IFN-γ did not differ in children with LTBI and TB either before or at the end of treatment. IGRA may remain positive over a long period of time. It seems that IGRA is not useful for monitoring treatment of children with LTBI and children with TB. Pediatr Pulmonol. © 2011 Wiley-Liss, Inc.

The clinical relevance of parallel detection of multiple viruses by real-time polymerase chain reaction (RT-PCR) remains unclear. This study evaluated the association between the detection of multiple viruses by RT-PCR and disease severity in children with bronchiolitis.

Children less than 2 years of age with clinical symptoms of bronchiolitis were prospectively included during three winter seasons. Patients were categorized in three groups based on disease severity; mild (no supportive treatment), moderate (supplemental oxygen and/or nasogastric feeding), and severe (mechanical ventilation). Multiplex RT-PCR of 15 respiratory viruses was performed on nasopharyngeal aspirates.

In total, 142 samples were obtained. Respiratory Syncytial virus (RSV) was the most commonly detected virus (73%) followed by rhinovirus (RV) (30%). In 58 samples (41%) more than one virus was detected, of which 41% was a dual infection with RSV and RV. In RSV infected children younger than 3 months, disease severity was not associated with the number of detected viruses. Remarkably, in children older than 3 months we found an association between more severe disease and RSV mono-infections.

Disease severity in children with bronchiolitis is not associated with infection by multiple viruses. We conclude that other factors, such as age, contribute to disease severity to a larger extent. Pediatr Pulmonol. © 2011 Wiley-Liss, Inc.

There is growing use of nasal continuous positive airway pressure ventilation (nCPAP) for infants with bronchiolitis, based on clinical assessment of severity. Despite this there have been no studies which identify clinical predictors for the requirement of nCPAP.

To identify clinical factors in infants with acute bronchiolitis in the emergency department (ED), which might predict a requirement for nCPAP following admission.

Retrospective review of pediatric ED case notes was conducted on bronchiolitis admissions to one dedicated Paediatric ED over a 12-month period. Potential predictors were identified through literature review. Data extraction of predictors was carried out and recorded for each case. Logistic regression was conducted for each variable to identify statistically significant predictors of nCPAP requirement.

Twenty-eight (17%) of the 163 admitted infants received nCPAP. The strongest predictors of nCPAP requirement in were as follows: oxygen requirement within the ED (P < 0.001), lower oxygen saturation (P < 0.001), younger age at presentation (P = 0.002), higher respiratory rate (P = 0.002), higher heart rate (P = 0.003), lower Glasgow Coma Scale score (0.006), and younger gestational age (P = 0.024).

We have identified clinical variables that were predictive of nCPAP requirement in infants admitted to our unit with bronchiolitis, oxygen requirement in the ED being the strongest single predictor. This is the first such study in the UK, and we hope it may be a starting point for further work that may provide an evidence base to aid clinicians in predicting the use of nCPAP in infants with bronchiolitis. Pediatr Pulmonol. © 2011 Wiley-Liss, Inc.

Asthma is the most common chronic inflammatory disease in childhood and some reports have demonstrated systemic inflammation. The relevance of high-sensitivity assays for C-reactive protein (hs-CRP), which are known to be a sensitive marker of low-grade systemic inflammation, has not been fully studied in childhood asthma.

This cross sectional case–control study aimed at evaluating serum hs-CRP in asthmatic children with different grades of severity and control.

Serum hs-CRP, sputum cytology study, and forced expiratory volume in 1 sec (FEV1) % of predicted for age and sex were estimated in 60 asthmatic children (30 uncontrolled steroid-naïve, and 30 controlled on inhaled steroid). They were recruited from Pediatric Chest Clinic, Children's Hospital, Ain Shams University. Sixty healthy children-age and sex-matched were included as a control group.

Serum hs-CRP concentrations were significantly higher in asthmatics than in controls with a median of 1.93 mg/L and 0.24 mg/L, respectively. Serum hs-CRP levels were significantly higher in uncontrolled steroid-naïve asthmatics than those controlled on inhaled steroid with a median of 3.15 mg/L and 1.55 mg/L, respectively. Serum hs-CRP showed a sensitivity of 72% and a specificity of 93%.

Despite that pulmonary function tests and clinical classification are the gold standard for grading of asthma, hs-CRP can be considered as a new marker for assessment of different grades of asthma severity and control. It can be used for indirect detection and monitoring of airway inflammation, disease severity, and response to steroid treatment in asthmatic children. Pediatr Pulmonol. 2012; 47:220–225. © 2011 Wiley Periodicals, Inc.

Asthma control represents a major challenge in the management of asthmatic children; however, correct perception of control is poor. The aim of the study was to evaluate the association between subjective answers given to the Childhood Asthma Control Test (C-ACT) and objective evaluation of exercise-induced bronchonstriction (EIB) by standardized treadmill exercise challenge.

EIB was evaluated by standardized treadmill exercise challenge and related to C-ACT scores in 92 asthmatic children.

Of the 92 studied children only six children had a concordance between a positive challenge test (ΔFEV1 ≥ 13%) and a positive response to the exercise-related issue of the C-ACT questionnaire (C-ACT total score ≤ 19). There was no significant association between the degree of EIB and the scores relative to the single question on exercise-related problems while a significant association was found when considering the whole questionnaire with C-ACT total score > 19 (r = −0.40, P < 0.001). The two single questions showing a significant association were those focusing on nocturnal asthma. The areas under the ROC curve (AUC) for the sum of the scores of these questions in relationship to a positive response to the exercise test was 0.74. The AUC of the C-ACT total score was 0.76 and 0.55 for the specific question on EIB related problems.

The discrimination power of the C-ACT total score in relationship to EIB was moderately good, and C-ACT questionnaire was capable of correctly predicting the absence of EIB in children reporting a global score > 19. However, direct questions on EIB are associated with a high number of false positive and negative responses; better associations are found questioning on the presence on nocturnal symptoms. Pediatr Pulmonol. 2012; 47:226–232. © 2011 Wiley Periodicals, Inc.

During severe exacerbations, asthmatic children vary significantly in their response to high-dose continuous β₂-adrenergic receptor (ADRβ₂) agonist therapy. Genetic polymorphisms have been identified within the ADRβ₂ that may be functionally relevant, but few studies have been performed in this population. Our hypothesis was that genotypic differences are associated with magnitude of response to ADRβ₂ agonist treatment during severe asthma exacerbations in children.

Children aged 2–18 years admitted to the ICU (intensive care unit) with a severe asthma exacerbation between 2006 and 2008 were eligible. Genotyping of the ADRβ₂ was performed.

Eighty-nine children consented and were enrolled. Despite similar clinical asthma scores on admission, children with the Gly¹⁶Gly genotype at amino acid position 16 had significantly shorter ICU length of stay (LOS) and hospital LOS, compared to children with Arg¹⁶Arg and Arg¹⁶Gly genotypes. Children with either the Gln²⁷Glu or Glu²⁷Glu genotype at amino acid position 27 also had significantly shorter ICU LOS and hospital LOS compared to children with the Gln²⁷Gln genotype. The Arg¹⁶Gly-Gln²⁷Gln haplotype was associated with the longest ICU LOS, but this was not statistically different from other haplotypes.

In this cohort of children with severe asthma exacerbations, ADRβ₂ polymorphisms were associated with responses to therapy. Knowledge of the genetic profile of children with asthma may allow for targeted therapy during acute exacerbations. Pediatr Pulmonol. 2012; 47:233–239. © 2011 Wiley Periodicals, Inc.

Adult cystic fibrosis (CF) patients are an expanding cohort that is taken care of in a variety of hospital settings including adult centers located within pediatric institutions. This study compared costs and discharge rates among adult CF patient hospitalizations in terms of location of hospitalization.

The 2007 Nationwide Inpatient Sample was utilized to identify adult CF patient admission data on patients aged 18–44. Data were separated into pediatric and adult facilities based on percentage discharge rate for patients >18. Primary outcomes measures were length of stay (LOS) and total hospital charges. Secondary predictors were geographic, primary payer, and co-morbidity effects on LOS and total hospital charges.

LOS was higher for adult CF patient admissions in pediatric facilities compared to adult facilities by a mean of 2.5 days. Mean total hospital charges were not significantly different. Adult hospitals in the Western U.S. had a mean total charge more than $50,000 greater than any region in the U.S. Self-pay patients had significantly fewer hospital days and charges across all hospital types. Adult facilities had 7% more CF patients discharged home with home healthcare use. Depressed CF patients had longer LOS by 1.5 days regardless of facility type.

LOS for adult CF inpatient admissions was significantly lower in adult facilities compared to pediatric facilities without a significant difference in hospital charges and is influenced by geographic hospital location. Depressed patients had longer lengths of stay regardless of facility type. Self-insured adult CF patients have a significant reduction in LOS and hospital charges when compared to all other payers regardless of hospital type. Pediatr Pulmonol. 2012; 47:245–251. © 2011 Wiley Periodicals, Inc.

We evaluated safety and efficacy of recombinant human growth hormone (rhGH) for improving growth, lean body mass (LBM), pulmonary function, and exercise tolerance in children with cystic fibrosis (CF) and growth restriction.

Multicenter, open-label, controlled clinical trial comparing outcomes in prepubertal children <14 years with CF, randomized in a 1:1 ratio to receive daily rhGH (Nutropin AQ) or no treatment (control) for 12 months, followed by a 6-month observation (month 18). Safety was monitored at each visit, including assessments of glucose tolerance.

Sixty-eight subjects were randomized (control n = 32; rhGH n = 36). Mean height standard deviation score (SDS) in the rhGH group increased by 0.5 ± 0.4 at 12 months (mean ± SD, P < 0.001); the control group height SDS remained unchanged. Weight increased by 3.8 ± 1.8 versus 2.8 ± 1.5 kg, (mean ± SD, P = 0.0356) and LBM increased by 3.8 ± 1.8 versus 2.1 ± 1.4 kg (P = 0.0002) in the rhGH group versus controls, respectively. Forced vital capacity increased by 325 ± 319 in the rhGH group compared with 178 ± 152 ml in controls (mean ± SD, P = 0.032). Forced expiratory volume in 1 sec improved in both groups with a significant difference between groups after adjustment for baseline severity (LS mean ± SE: rhGH, 224 ± 37, vs. controls, 108 ± 40 ml; P = 0.04). There was no difference between groups in exercise tolerance (6-min walk distance) at 1 year. Changes in glucose tolerance for the two groups were similar over the 12-month study period, with three subjects developing IGT and one CFRD in each group. One rhGH-treated patient developed increased intracranial pressure.

Treatment with rhGH in prepubertal children with CF was effective in promoting growth, weight, LBM, lung volume, and lung flows, and had an acceptable safety profile. Pediatr Pulmonol. 2012; 47:252–263. © 2011 Wiley Periodicals, Inc.

Chronic lung disease of prematurity (CLDP) is a frequent complication of premature birth. Infants and children with CLDP are often prescribed complex medication regimens, which can be difficult for families to manage.

We sought to determine whether non-adherence was associated with increased CLDP-related morbidities and to identify predictors of adherence.

Recruited caregivers of 194 children with CLDP completed questionnaires regarding self-reported adherence, respiratory outcomes, and quality of life (January 2008–June 2010). Adherence data were available for 176 subjects, of whom 143 had self-reported data only, and 33 had prescription claims data, which were used to calculate a medication possession ratio (MPR). Participants in the Prescription Claims Sample (n = 33) were more likely to have public insurance (P < 0.001).

Self-reported adherence substantially overestimated medication possession; the mean MPR was 38.8% (n = 33) and was not associated with self-reported adherence (P = 0.71; n = 26). In a small sample, higher MPR was associated with decreased odds ratios of visiting the emergency department (ED) (OR = 0.75 for a 10% increase in MPR [95%CI: 0.58, 0.97]; P = 0.03; n = 74 questionnaires from 28 participants), activity limitations (OR = 0.71 [95%CI: 0.53, 0.95]; P = 0.02; n = 70 questionnaires from 28 participants), and rescue medication use (OR = 0.84 [95%CI: 0.73-0.98]; P = 0.03; n = 70 questionnaires from 28 participants). Increasing caregiver worries regarding medication efficacy and side effects were associated with lower MPR (P = 0.04 and 0.02, respectively; n = 62 questionnaires from 27 participants). Socio-demographic and clinical risk factors were not predictors of MPR (n = 33).

We found that non-adherence with respiratory medications was common in premature infants and children with CLDP. Using multiple timepoints in a small sample, non-adherence was associated with a higher likelihood of respiratory morbidities. Although self-reported adherence and demographic characteristics did not predict MPR, concerns about medications did. We suggest that addressing caregiver concerns about medications may improve adherence and ultimately decrease CLDP-related morbidities. Larger, prospective studies are needed to confirm these findings and determine which factors predict non-adherence. Pediatr Pulmonol. 2012; 47:283–291. © 2011 Wiley Periodicals, Inc.

The pathobiology of ventilator-associated pneumonia (VAP) in children is poorly understood; investigation has been limited by lack of universally applied diagnostic criteria and reliable biomarkers for this condition.

We evaluated the clinical pulmonary infection score (CPIS) in diagnosing VAP and prospectively characterized the relationship between surfactant protein-D (SP-D) metabolism and VAP.

Children admitted to an Egyptian PICU requiring intubation were screened for the absence of primary pulmonary pathology. Thirty-nine children underwent two evaluations: during the first 36 hr following intubation and after 4 days of mechanical ventilation. During both, bronchoalveolar lavage fluid (BALF) was obtained for culture and SP-D assay. CPIS was computed during the second evaluation.

Optimum performance of the CPIS against BALF culture occurred at a cutoff value of 6, (ROC AUC of 0.89 ± 0.05). Children who developed VAP had significantly higher SP-D levels, both preceding (129.9 ± 33.5 ng/ml at the 1st BAL)—and following positive BALF culture (249.5 ± 51.2 ng/ml at the 2nd BAL), compared to children whose BALF remained sterile (62.6 ± 18.1 ng/ml and 64.9 ± 9.4 ng/ml; P < 0.001). This increase in SP-D levels was most evident in children infected with Pseudomonas aeruginosa compared to children with Klebsiella pneumonia or S. aureus.

The CPIS performed well against BALF culture. We observed a bacterial species-specific difference in SP-D levels in children who developed VAP; this change preceded detection of infection by CPIS or BALF culture. Pediatr Pulmonol. 2012; 47:292–299. © 2011 Wiley Periodicals, Inc.