Exhaled nitric oxide measurements in the first 2 years of life: methodological issues, clinical and epidemiological applications

Fractional exhaled nitric oxide (FeNO) is a useful tool to diagnose and monitor eosinophilic bronchial inflammation in asthmatic children and adults. In children younger than 2 years of age FeNO has been successfully measured both with the tidal breathing and with the single breath techniques. However, there are a number of methodological issues that need to be addressed in order to increase the reproducibility of the FeNO measurements within and between infants. Indeed, a standardized method to measure FeNO in the first 2 years of life would be extremely useful in order to meaningfully interpret FeNO values in this age group. Several factors related to the measurement conditions have been found to influence FeNO, such as expiratory flow, ambient NO and nasal contamination. Furthermore, the exposure to pre- and postnatal risk factors for respiratory morbidity has been shown to influence FeNO values. Therefore, these factors should always be assessed and their association with FeNO values in the specific study population should be evaluated and, eventually, controlled for

DNase treatment for atelectasis in infants with severe respiratory syncytial virus bronchiolitis

Respiratory insufficiency due to respiratory syncytial virus (RSV) bronchiolitis is partly due to the abundance of thickened mucus and the inability to clear it from the airways. Mucus in RSV bronchiolitis contains necrotic inflammatory and epithelial cells. The viscoelastic properties of purulent airway secretions are largely due to the presence of highly polymerized deoxyribonucleic acid (DNA). Recombinant human deoxyribonuclease (rhDNase) is known to liquefy such mucus in patients with cystic fibrosis, whereas case reports described a beneficial effect in other respiratory disorders. The authors hypothesized that rhDNase would diminish atelectasis and mucus plugging in infants with severe RSV bronchiolitis. Two infants with RSV bronchiolitis with massive unilateral atelectasis in whom mechanical ventilation was imminent due to exhaustion, and three mechanically ventilated infants (two neonates, one with bronchopulmonary dysplasia) with RSV bronchiolitis with pneumonia received treatment with 2.5 mg nebulized rhDNase twice daily. Following administration of nebulized recombinant human deoxyribonuclease, clinical and radiological parameters improved quickly. Mechanical ventilation could be avoided in two infants while in three infants on artificial ventilation, clinical recovery started following the first dose of the drug. A therapeutic trial of recombinant human deoxyribonuclease may be an option in the treatment for atelectasis in severe or

Prospective longitudinal evaluation of lung function during the first year of life after repair of congenital diaphragmatic hernia

OBJECTIVE: To evaluate lung function and respiratory morbidity prospectively during the first year of life in patients with congenital diaphragmatic hernia and to study the effect of extracorporeal membrane oxygenation therapy. DESIGN: Prospective longitudinal cohort study. SETTING: Outpatient clinic of a tertiary-level pediatric hospital. PATIENTS: The cohort of 43 infants included 12 patients treated with extracorporeal membrane oxygenation. Evaluation was at 6 and 12 months; 33 infants were evaluated at both time points. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Maximal expiratory flow at functional residual capacity and functional residual capacity were measured with Masterscreen Babybody. Z-scores were calculated for maximal expiratory flow at functional residual capacity. Mean maximal expiratory flow at functional residual capacity values at 6 and 12 months were significantly below the expected values (mean z-score -1.4 and -1.5, respectively) without a significant change between both time points. Values did not significantly differ between extracorporeal membrane oxygenation and nonextracorporeal membrane oxygenation-treated patients. Functional residual capacity values were generally high, 47% were above the suggested normal range, and did not change significantly over time. Mean functional residual capacity values in extracorporeal membrane oxygenation-treated patients were significantly higher than in nonextracorporeal membrane oxygenation-treated patients (p = .006). The difference (5.1 mL/kg ± 1.8 SE) did not change significantly between the two time points. Higher mean airway pressure and longer duration of ventilation were associated with higher functional residual capacity. None of the perinatal characteristics was associated with maximal expiratory flow at functional residual capacity. Mean weight z-scores were significantly below zero at both time points (p < .001). Mean weight z-score in extracorporeal membrane oxygenation-treated patients were lower than in nonextracorporeal membrane oxygenation-treated patients (p = .046). CONCLUSIONS: Infants with congenital diaphragmatic hernia have decreased expiratory flows and increased functional residual capacity within the first year of life. Extracorporeal membrane oxygenation-treated patients with congenital diaphragmatic hernia may have more respiratory morbidity and concomitant growth impairment. Close follow-up beyond the neonatal period is therefore required. Copyrigh

Brand and generic use of inhalation medication and frequency of switching in children and adults : a population-based cohort study

BACKGROUND: The expiration of patents of brand inhalation medications and the ongoing pressure on healthcare budgets resulted in a growing market for generics. AIM: To study the use of brand and generic inhalation medication and the frequency of switching between brand and generic and between devices. In addition, we investigated whether switching affected adherence. METHODS: From dispensing data from the Dutch PHARMO Database Network a cohort aged ≥ 5 years, using ≥ 1 year of inhalation medication between 2003 and 2012 was selected. Switching was defined as changing from brand to generic or vice versa. In addition, we studied change in aerosol delivery device type (e.g., DPI, pMDI, and nebulizers). Adherence was calculated using the medication possession ratio (MPR). RESULTS: The total cohort comprised 70,053 patients with 1,604,488 dispensations. Per calendar year, 5% switched between brand and generic inhalation medication and 5% switched between devices. Median MPRs over the first 12 months ranged between 33 and 55%. Median MPR over the total period was lower after switch from brand to generic and vice versa for formoterol (44.5 vs. 42.1 and 63.5 vs. 53.8) and beclomethasone (93.8 vs. 59.8 and 81.3 vs. 55.9). CONCLUSION: Per year, switching between brand and generic inhalation medication was limited to 5% of the patients, switching between device types was observed in 5% as well. Adherence to both generic and brand inhalation medication was low. Effect of switching on adherence was contradictory; depending on time period, medication and type, and direction of switching. Further research on reasons for switching and potential impact on clinical outcomes is warranted

Reported versus measured body weight and height of 4-year-old children and the prevalence of overweight

Background: In adults, body weight tends to be underestimated when based on self-reported data. Whether this discrepancy between measured and reported data exists in healthy young children is unclear. We studied whether parental reported body weight and height of 4-year-old children corresponded with measured body weight and height. In addition, we studied the determinants and the consequences of differences between reported and measured data. Methods: Data on body weight and height of 864 4-year-old Dutch children born in 1996/1997 enrolled in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study were collected via a questionnaire and a medical examination. Overweight was defined according to standard international age and gender specific definitions. Results: Mean differences between measured and reported body weight, height, and body mass index (BMI) were small. Parents of children with a low BMI tended to over report body weight while parents of children with a high BMI tended to underreport body weight. Whereas 9.5% of the children were overweight according to reported BMI, the prevalence of overweight was 13.4% based on measured BMI. Over 45% of the overweight children according to measured BMI were missed when reported BMI was used. Conclusion: These findings suggest that overweight prevalence rates in children are underestimated when based on reported weight and height

Lung eicosanoids in perinatal rats with congenital diaphragmatic hernia

Abnormal levels of pulmonary eicosanoids have been reported in infants with persistent pulmonary hypertension (PPH) and congenital diaphragmatic hernia (CDH). We hypothesized that a dysbalance of vasoconstrictive and vasodilatory eicosanoids is involved in PPH in CDH patients. The levels of several eicosanoids in lung homogenates and in bronchoalveolar lavage fluid of controls and rats with CDH were measured after caesarean section or spontaneous birth. In controls the concentration of the stable metabolite of prostacyclin (6-keto-PGF1α), thromboxane A2 (TxB2), prostaglandin E2 (PGE2), and leukotriene B4 (LTB4) decreased after spontaneous birth. CDH pups showed respiratory insufficiency directly after birth. Their lungs had higher levels of 6- keto-PGF1α, reflecting the pulmonary vasodilator prostacyclin (PGI2), than those of controls. We conclude that in CDH abnormal lung eicosanoid levels are present perinatally. The elevated levels of 6-keto-PGF1α in CDH may reflect a compensation mechanism for increased vascular resistance

Psychometric properties of the Minnesota Living with Heart Failure Questionnaire (MLHF-Q)

Objective: To evaluate the psychometric properties of the Minnesota Living with Heart Failure Questionnaire (MLHF-Q) in patients with atrial fibrillation. Design: A prospective study of the patients who underwent DC electrical cardioversion. Setting: Clinics of cardiology and thoracic surgery of the University Hospital in Groningen, the Netherlands. Main outcome measures: The disease-specific MLHF-Q and generic measures of quality of life were administered. The sensitivity to change over time was tested with effect sizes (ES). Internal consistency of MLHF-Q scales was estimated with Cronbach's alpha. To evaluate the construct validity multitrait-multimethod analysis was applied. The 'known group validity' was evaluated by the comparison of mean scores and effect sizes between two groups of the New York Heart Association (NYHA) classification (NYHA I versus II-III). Stability of MLHF-Q scales was estimated in a subgroup of patients who remained stable. Perfect congruence analysis and factor analysis were applied to confirm the a priori determined structure. Results: Cronbach's alpha was :0.80 of the MLHF-Q scales. Perfect congruence analysis (PCA) showed that the results resemble quite well the a priori assumed factor structure. Multitrait-multi method analysis showed convergent validity coefficients ranging from 0.59 to 0.73 (physical impairment dimension) and 0.39 to 0.69 (emotional dimension). The magnitude of change can be interpreted as medium (ES = 0.50). The results of a 'test-retest' analysis in a stable group can be valued as satisfactory for the MLHF-Q scales (Pearson's r > 0.60). The physical dimension and the overall score of the MLHF-Q discriminated significantly between the NYHA I and II-III groups (p <0.001) with large effect sizes (ES > 1.0). Conclusions: The MLHF-Q has solid psychometric properties and the outcome of the current study indicates that the MLHF-Q is an effective and efficient instrument