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

Exhaled nitric oxide in mylar balloons: influence of storage time, humidity and temperature.

BACKGROUND: Mylar balloons are used to collect exhaled air for analysis of fractional nitric oxide concentration (FENO). AIM: We studied the effect of storage conditions on the stability of nitric oxide (NO) in mylar balloons. METHODS: Exhaled air samples and calibration gases were stored in mylar balloons at 4, 21 and 37 degrees C, with or without silica gel. NO was measured after 0, 6, 9, 24 and 48 h. Scheffe F-tests were used to compare NO values. RESULTS: NO remained stable in balloons for 9 h at all temperatures, without silica gel. NO increased between 9 and 48 h, but only with low initial FENO. Silica gel increased variability. CONCLUSIONS: FENO in mylar balloons is stable for at least 9 h. The storage temperature is not critical, but silica gel increases variability

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

Pro-inflammatory cytokines induce c-fos expression followed by IL-6 release in human airway smooth muscle cells

BACKGROUND: Airway smooth muscle (ASM) is considered to be a target for mediators released during airway inflammation. AIMS: To investigate the expression of c-fos, a constituent of the transcription factor activator protein-1, in human ASM cells. In addition, to measure the release of interleukin (IL)-6 into the conditioned medium of stimulated ASM cells, as well as DNA biosynthesis and changes in cell number. METHODS: Serum-deprived human ASM cells in the G0/G1 phase were stimulated with the pro-inflammatory cytokines; tumour necrosis factor-alpha, IL-1beta, IL-5 and IL-6. The expression of mRNA encoding the proto-oncogene c-fos was measured by Northern blot analysis. Cell proliferation was assessed by [3H]-thymidine incorporation assays and cell counting, and IL-6 levels in cell-conditioned medium were measured by enzyme-linked immunosorbent assay. RESULTS: All of the cytokines investigated induced a rapid (within 1 h) and transient increase in the expression of mRNA encoding c-fos, followed by the expression and enhanced release of IL-6. Cell proliferation remained unchanged in cytokine-stimulated cells. CONCLUSIONS: Cytokine-induced c-fos expression in human ASM cells could be described as a marker of cell 'activation'. The possible association of these results with airway inflammation, through secondary intracellular mechanisms such as cytokine production, is discussed

Air pollution and airway resistance at age 8 years - the PIAMA birth cohort study.

Air pollution has been found to adversely affect children's lung function. Forced expiratory volume in 1 s and forced vital capacity from spirometry have been studied most frequently, but measurements of airway resistance may provide additional information. We assessed associations of long-term air pollution exposure with airway resistance

Quality of life and psychosocial outcomes in children with severe acute asthma and their parents

Objectives: To prospectively evaluate quality of life (QoL) and psychosocial outcomes in children with severe acute asthma (SAA) after pediatric intensive care (PICU) admission compared to children with SAA who were admitted to a general ward (GW). In addition, we assessed posttraumatic stress (PTS) and asthma-related QoL in the parents. Methods: A preplanned follow-up of 3 to 9 months of our nationwide prospective multicenter study, in which children with SAA admitted to a Dutch PICU (n = 110) or GW (n = 111) were enrolled between 2016 and 2018. Asthma-related QoL, PTS symptoms, emotional and behavioral problems, and social impact in children and/or parents were assessed with validated web-based questionnaires. Results: We included 100 children after PICU and 103 after GW admission, with a response rate of 50% for the questionnaires. Median time to follow-up was 5 months (range: 1-12 months). Time to reach full schooldays after admission was significantly longer in the PICU group (mean of 10 vs 4 days, P =.001). Parents in the PICU group reported more PTS symptoms (intrusion P =.01, avoidance P =.01, arousal P =.02) compared to the GW group. Conclusion: No significant differences were found between PICU and GW children on self-reported outcome domains, except for the time to reach full schooldays. PICU parents reported PTS symptoms more often than the GW group. Therefore, monitoring asthma symptoms and psychosocial screening of children and parents after PICU admission should both be part of standard care after SAA. This should identify those who are at risk for developing PTSD, to timely provide appropriate interventions

Eczema phenotypes and risk of allergic and respiratory conditions in school age children

Background: Eczema phenotypes based on eczema onset and persistence might better identify groups prone to allergic and respiratory conditions than a binary definition of eczema. We examined the associations of childhood eczema phenotypes with allergic sensitization, allergy, asthma and lung function at school age. Methods: This study among 4277 children was embedded in a multi-ethnic population-based prospective cohort study. Five eczema phenotypes (never, early transient, mid-transient, late transient, persistent) based on parental-reported physician-diagnosed eczema from age 6 months until 10 years were identified. At age 10 years, allergic sensitization was measured by skin prick tests, physician-diagnosed allergy and asthma by parent-reported questionnaires, and lung function by spirometry. Adjusted linear, logistic and multinomial regression models were applied. Results: Compared with never eczema, all eczema phenotypes were associated with increased risks of asthma (odds ratios (OR) range (95% confidence interval): 2.68 (1.58, 4.57) to 11.53 (6.65, 20.01)), food and inhalant allergic sensitization (1.72 (1.25, 2.36) to 12.64 (7.20, 22.18)), and physician-diagnosed inhalant allergy (1.92 (1.34, 2.74) to 11.91 (7.52, 18.86)). Strongest effect estimates were observed of early and persistent eczema with the risk of physician-diagnosed food allergy (OR 6.95 (3.76, 12.84) and 35.05 (18.33, 70.00), respectively) and combined asthma and physician-diagnosed allergy (7.11 (4.33, 11.67) and 29.03 (15.27, 55.22), respectively). Eczema phenotypes were not associated with lung function measures. Conclusion: Eczema phenotypes were differentially associated with risks of respiratory and allergic conditions in school-aged children. Children with early transient and persistent eczema might benefit from more intense follow-up for early identification and treatment of asthma and allergies