The influence of sighing respirations on infant lung function measured using multiple breath washout gas mixing techniques

There is substantial interest in studying lung function in infants, to better understand the early life origins of chronic lung diseases such as asthma. Multiple breath washout (MBW) is a technique for measuring lung function that has been adapted for use in infants. Respiratory sighs occur frequently in young infants during natural sleep, and in accordance with current MBW guidelines, result in exclusion of data from a substantial proportion of testing cycles. We assessed how sighs during MBW influenced the measurements obtained using data from 767 tests conducted on 246 infants (50% male; mean age 43 days) as part of a large cohort study. Sighs occurred in 119 (15%) tests. Sighs during the main part of the wash‐in phase (before the last 5 breaths) were not associated with differences in standard MBW measurements compared with tests without sighs. In contrast, sighs that occurred during the washout were associated with a small but discernible increase in magnitude and variability. For example, the mean lung clearance index increased by 0.36 (95% CI: 0.11–0.62) and variance increased by a multiplicative factor of 2 (95% CI: 1.6–2.5). The results suggest it is reasonable to include MBW data from testing cycles where a sigh occurs during the wash‐in phase, but not during washout, of MBW. By recovering data that would otherwise have been excluded, we estimate a boost of about 10% to the final number of acceptable tests and 6% to the number of individuals successfully tested

Effect of egg turning and incubation time on carbonic anhydrase gene expression in the blastoderm of the Japanese quail (Coturnix c. japonica)

(1) The gene expression of carbonic anhydrase, a key enzyme for the production sub-embryonic fluid (SEF), was assessed in turned and unturned eggs of the Japanese quail. The plasma membrane-associated isoforms CA IV, CAIX, CA XII, CA XIV, and the cytoplasmic isoform CA II, were investigated in the extra-embryonic tissue of the blastoderm and in embryonic blood. (2) Eggs were incubated at 37.6C, c. 60% R.H., and turned hourly (90 ) or left unturned. From 48 to 96 hours of incubation mRNA was extracted from blastoderm tissue, reverse-transcribed to cDNA and quantified by real-time qPCR using gene-specific primers. Blood collected at 96h was processed identically. (3) Blastoderm CAIV gene expression increased with the period of incubation only in turned eggs, with maxima at 84 and 96h of incubation. Only very low levels were found in blood. (4) Blastoderm CA II gene expression was greatest at 48 and 54h of incubation, subsequently declining to much lower levels and una ected by turning. Blood CA II gene expression was about 25-fold greater than that in the blastoderm. (5) The expression of CA IX in the blastoderm was the highest of all isoforms, yet unaffected by turning. CA XII did not amplify and CA XIV was present at unquantifiable low levels. (6) It is concluded that solely gene expression for CA IV is sensitive to egg turning, and that increased CA IV gene expression could account for the additional SEF mass found at 84-96h of incubation. in embryos of turned eggs

Severity and persistence of asthma and mental health: a birth cohort study

Background. The goal of the current study was to investigate asthma and mental health among youth in the community, and to consider the role of asthma severity and persistence in this link

Development of a questionnaire-based insecticide exposure assessment method and comparison with urinary insecticide biomarkers in young Australian children

Environmental and behavioural factors assessed via an online questionnaire were compared to insecticide metabolite concentrations in urine collected from 61 children from South East Queensland, Australia. Metabolite concentrations (μg/L urine) were transformed using the natural logarithm prior to regression analysis and adjusted for age and creatinine. A significant dietary association was reported for vegetable intake and 3-phenoxybenzoic acid (3-PBA) (β: 1.47 for top quartile of intake versus bottom quartile of intake 95% CI: 0.36, 2.57). Intake of vegetables and fruit were also positively associated with sum non-specific organophosphate metabolites (ƩnsOP). ƩnsOP concentrations were lower when fruits and vegetables were always or almost always washed prior to cooking or eating (β: -0.69 95% CI: -1.25, -0.12). In multivariable modelling 3-PBA concentrations were also associated with hand-washing frequency (β: 1.69 95% CI: 0.76, 2.61 for  3 day), presence of a dog in the home (β: 0.73 95% CI: 0.07, 1.38), frequency of pest-spray use in the summer months (β: 0.88 95% CI: 0.22, 1.54 weekly versus less than weekly) and season (β: 0.88 95% CI: 0.32, 1.44 for spring/summer versus winter/autumn). This is the first study in Australia to report dietary, behavioural and environmental factors associated with biomarkers of insecticide exposure in young children

Oxidation contributes to low glutathione in the airways of children with cystic fibrosis

Glutathione is an important antioxidant in the lungs but its concentration is low in the airways of patients with cystic fibrosis. Whether this deficit occurs from an early age or how oxidative stress contributes to lowering glutathione is unknown. We measured glutathione, its oxidation products, myeloperoxidase, and biomarkers of hypochlorous acid in bronchoalveolar lavage from children with cystic fibrosis and disease controls using mass spectrometry and immunological techniques. The concentration of glutathione was lower in bronchoalveolar lavage from children with cystic fibrosis, whereas glutathione sulfonamide, a specific oxidation product of hypochlorous acid, was higher. Oxidised glutathione and glutathione sulfonamide correlated with myeloperoxidase and a biomarker of hypochlorous acid. The percentage of glutathione attached to proteins was higher in children with cystic fibrosis than controls. Pulmonary infections in cystic fibrosis resulted in lower levels of glutathione but higher levels of oxidised glutathione and glutathione sulfonamide in bronchoalveolar lavage. The concentration of glutathione is low in the airways of patients with cystic fibrosis from an early age. Increased oxidation of glutathione by hypochlorous acid and its attachment to proteins contribute to this deficiency. Therapies targeted against myeloperoxidase may boost antioxidant defence and slow the onset and progression of lung disease in cystic fibrosis

The importance of the local environment in the transmission of respiratory syncytial virus

The role of the environment in the spread of respiratory infections is poorly understood, and consequently probably underappreciated. To improve our understanding of the environmental drivers of respiratory syncytial virus (RSV) transmission, we examined RSV seasonality in two settings with unusual seasonal patterns: The Gambia (where RSV epidemics occur at different times of the year) and Southeast Florida (where RSV seasonality differs from the rest of mainland USA). We used published data to correlate the seasonality of RSV with rainfall and child nutrition in the Gambia, and with rainfall and temperature in Florida. In the Gambia, RSV incidence was more strongly and more consistently correlated with child nutrition (r=.0.73 [95%CI0.90 to 0.38]) than with rainfall (r=0.37 [95%CI 0.20 to 0.52]). In Southeast Florida RSV incidence was strongly correlated with rainfall two months previously (r=0.65 [95%CI 0.40 to 0.81]) compared to North Florida where RSV incidence was strongly correlated with temperature (r=0.75 [95%CI 0.87 to 0.56]). We propose that nutrition is the dominant environmental driver of RSV seasonality in the Gambia, while rainfall is the dominant driver of RSV seasonality in Southeast Florida. This reinforces the importance of an ecological scale understanding of disease transmission: only with such an evidence base can setting-specific recommendations be made for public health interventions that are targeted for maximum efficacy

Reversal of airway hyperresponsiveness by induction of airway mucosal CD4+CD25+ regulatory T cells

An important feature of atopic asthma is the T cell–driven late phase reaction involving transient bronchoconstriction followed by development of airways hyperresponsiveness (AHR). Using a unique rat asthma model we recently showed that the onset and duration of the aeroallergen-induced airway mucosal T cell activation response in sensitized rats is determined by the kinetics of functional maturation of resident airway mucosal dendritic cells (AMDCs) mediated by cognate interactions with CD4+ T helper memory cells. The study below extends these investigations to chronic aeroallergen exposure. We demonstrate that prevention of ensuing cycles of T cell activation and resultant AHR during chronic exposure of sensitized rats to allergen aerosols is mediated by CD4+CD25+Foxp3+LAG3+ CTLA+CD45RC+ T cells which appear in the airway mucosa and regional lymph nodes within 24 h of initiation of exposure, and inhibit subsequent Th-mediated upregulation of AMDC functions. These cells exhibit potent regulatory T (T reg) cell activity in both in vivo and ex vivo assay systems. The maintenance of protective T reg activity is absolutely dependent on continuing allergen stimulation, as interruption of exposure leads to waning of T reg activity and reemergence of sensitivity to aeroallergen exposure manifesting as AMDC/T cell upregulation and resurgence of T helper 2 cytokine expression, airways eosinophilia, and AHR

Sunshine, rainfall, humidity and child pneumonia in the tropics: time-series analyses

Few studies have formally examined the relationship between meteorological factors and the incidence of child pneumonia in the tropics, despite the fact that most child pneumonia deaths occur there. We examined the association between four meteorological exposures (rainy days, sunshine, relative humidity, temperature) and the incidence of clinical pneumonia in young children in the Philippines using three time-series methods: correlation of seasonal patterns, distributed lag regression, and case-crossover. Lack of sunshine was most strongly associated with pneumonia in both lagged regression [overall relative risk over the following 60 days for a 1-h increase in sunshine per day was 0·67 (95% confidence interval (CI) 0·51–0·87)] and case-crossover analysis [odds ratio for a 1-h increase in mean daily sunshine 8–14 days earlier was 0·95 (95% CI 0·91–1·00)]. This association is well known in temperate settings but has not been noted previously in the tropics. Further research to assess causality is needed