Comparative sensitivity of early cystic fibrosis lung disease detection tools in school aged children.

BACKGROUND: Effective detection of early lung disease in cystic fibrosis (CF) is critical to understanding early pathogenesis and evaluating early intervention strategies. We aimed to compare ability of several proposed sensitive functional tools to detect early CF lung disease as defined by CT structural disease in school aged children. METHODS: 50 CF subjects (mean±SD 11.2 ± 3.5y, range 5-18y) with early lung disease (FEV1≥70 % predicted: 95.7 ± 11.8 %) performed spirometry, Multiple breath washout (MBW, including trapped gas assessment), oscillometry, cardiopulmonary exercise testing (CPET) and simultaneous spirometer-directed low-dose CT imaging. CT data were analysed using well-evaluated fully quantitative software for bronchiectasis and air trapping (AT). RESULTS: CT bronchiectasis and AT occurred in 24 % and 58 % of patients, respectively. Of the functional tools, MBW detected the highest rates of abnormality: Scond 82 %, MBWTG RV 78 %, LCI 74 %, MBWTG IC 68 % and Sacin 51 %. CPET VO2peak detected slightly higher rates of abnormality (9 %) than spirometry-based FEV1 (2 %). For oscillometry AX (14 %) performed better than Rrs (2 %) whereas Xrs and R5-19 failed to detect any abnormality. LCI and Scond correlated with bronchiectasis (r = 0.55-0.64, p < 0.001) and AT (r = 0.73-0.74, p < 0.001). MBW-assessed trapped gas was detectable in 92 % of subjects and concordant with CT-assessed AT in 74 %. CONCLUSIONS: Significant structural and functional deficits occur in early CF lung disease, as detected by CT and MBW. For MBW, additional utility, beyond that offered by LCI, was suggested for Scond and MBW-assessed gas trapping. Our study reinforces the complementary nature of these tools and the limited utility of conventional oscillometry and CPET in this setting.

In utero smoking exposure induces changes to lung clearance index and modifies risk of wheeze in infants.

BACKGROUND: Fetal exposure to tobacco smoking throughout pregnancy is associated with wheezing in infancy. We investigated the influence of in utero smoking exposure on lung ventilation homogeneity and the relationship between lung ventilation inhomogeneity at 7 weeks of age and wheezing in the first year of life. METHODS: Maternal smoking was defined as self-reported smoking of tobacco or validated by exhaled (e)CO > 6 ppm. Lung function data from healthy infants (age 5-9 weeks) born to asthmatic mothers and parent-reported respiratory questionnaire data aged 12 months were collected in the Breathing for Life Trial (BLT) birth cohort. Tidal breathing analysis and SF6-based Multiple Breath Washout testing were performed in quiet sleep. Descriptive statistics and regression analysis were used to assess associations. RESULTS: Data were collected on 423 participants. Infants born to women who self-reported smoking during pregnancy (n = 42) had higher lung clearance index (LCI) than those born to nonsmoking mothers (7.90 vs. 7.64; p = .030). Adjusted regression analyzes revealed interactions between self-reported smoking and LCI (RR: 1.98, 95% CI: 1.07-3.63, 0.028, for each unit increase in LCI) and between eCO > 6 ppm and LCI (RR: 2.25, 95% CI: 1.13-4.50, 0.022) for the risk of wheeze in the first year of life. CONCLUSION: In utero tobacco smoke exposure induces lung ventilation inhomogeneities. Furthermore, an interaction between smoke exposure and lung ventilation inhomogeneities increases the risk of having a wheeze in the first year of life.

Clinical and Experimental Determination of Protection Afforded by BCG Vaccination against Infection with Non-Tuberculous Mycobacteria: A Role in Cystic Fibrosis?

Mycobacterium abscessus is a nontuberculous mycobacterium (NTM) of particular concern in individuals with obstructive lung diseases such as cystic fibrosis (CF). Treatment requires multiple drugs and is characterised by high rates of relapse; thus, new strategies to limit infection are urgently required. This study sought to determine how Bacille Calmette-Guérin (BCG) vaccination may impact NTM infection, using a murine model of Mycobacterium abscessus infection and observational data from a non-BCG vaccinated CF cohort in Sydney, Australia and a BCG-vaccinated CF cohort in Cape Town, South Africa. In mice, BCG vaccination induced multifunctional antigen-specific CD4+ T cells circulating in the blood and was protective against dissemination of bacteria to the spleen. Prior infection with M. abscessus afforded the highest level of protection against M. abscessus challenge in the lung, and immunity was characterised by a greater frequency of pulmonary cytokine-secreting CD4+ T cells compared to BCG vaccination. In the clinical CF cohorts, the overall rates of NTM sampling during a three-year period were equivalent; however, rates of NTM colonisation were significantly lower in the BCG-vaccinated (Cape Town) cohort, which was most apparent for M. abscessus. This study provides evidence that routine BCG vaccination may reduce M. abscessus colonisation in individuals with CF, which correlates with the ability of BCG to induce multifunctional CD4+ T cells recognising M. abscessus in a murine model. Further research is needed to determine the optimal strategies for limiting NTM infections in individuals with CF.

Changes in the Presence of Nonnutritive Sweeteners, Sugar Alcohols, and Free Sugars in Australian Foods.

BACKGROUND: In parallel with growing consumer interest in reducing sugar intake, manufacturers have increased availability of food and beverage products containing nonnutritive sweeteners (NNSs). However, emerging evidence indicates that specific NNS types have differential effects on cardiometabolic health. OBJECTIVE: This study examined overall changes in the presence of NNSs, sugar alcohols, and free sugars in the Australian food supply and the use of specific NNS types. PARTICIPANTS/SETTING: Data for 21,051 products in 2015 and 21,366 products in 2019 were extracted from The George Institute's FoodSwitch database. MAIN OUTCOME MEASURES: The proportion of products containing NNSs, sugar alcohols, free sugars, and a combination of these, as well as proportion of products containing specific NNS types. STATISTICAL ANALYSES PERFORMED: Changes between 2015 and 2019 were examined using Pearson χ2 tests. RESULTS: Between 2015 and 2019, there was a significant increase in the proportion of food and beverage products containing NNSs (from 3.8% to 4.3%; P < .001) and a significant decrease in products containing free sugars (from 62.7% to 59.9%; P < .001),) driven primarily by nondairy beverages. There were changes in the use of specific NNS types between 2015 and 2019, with a large increase in the use of steviol glycosides (from 33.7% to 50.2%) and a large decrease in the use of sucralose (from 42.4% to 30.5%), aspartame (from 21.0% to 14.4%), and acesulfame K (from 57.4% to 27.7%) (P < .05 for all). CONCLUSIONS: These findings on the use of different NNS, sugar alcohol, and free sugar ingredients and combinations provide important research insights and will be useful in informing government policies that address sugars and other sweeteners in Australian foods.

'Life-changing surgery': English-language news media representation of selective dorsal rhizotomy.

BACKGROUND: Selective dorsal rhizotomy (SDR) is a neurosurgical intervention to reduce spasticity in children with cerebral palsy. Parents researching SDR for their child may be influenced by framing of SDR in news media articles they read. This study examined framing of SDR in English-language news media. METHODS: Content analysis of English-language news media articles including the search term 'rhizotomy' in the Factiva database published July 2015 to July 2018 in online or print form in Canada, New Zealand, Australia, United States of America and the United Kingdom. RESULTS: One hundred and eighty-six articles were identified describing 91 different children (45 male), almost all with cerebral palsy, median age 4 years old. One hundred and twenty-six articles were written prior to surgery; in many articles, SDR surgery involved travel overseas and/or fundraising. SDR was described universally in positive terms with little discussion of risks. Content of articles variably included the specialized nature of SDR, parental frustration with their local health system and their hope for positive outcomes. There was geographical variation in both numbers of articles and content. CONCLUSIONS: SDR is a common focus in cerebral palsy news media articles in some countries. Framing in these articles supports SDR as a beneficial and specialized procedure and may lead families to believe they need to work outside their local health systems. As news media are likely an important influence on families' attitudes to SDR, clinicians should be aware of this influence.