Hiran Selvadurai

Normal Development of the Lung and Premature Birth

The following review focuses on the normal development of the lung from conception to birth. The defined periods of lung development-Embryonic, Pseudoglandular, Canalicular, Saccular and Alveolar-will be explored in detail in relation to gestational age. Cellular differentiation, formation of the conducting airways and respiratory zone and development of the alveoli will be reviewed. Pulmonary vascular development will also be examined within these periods to relate the formation of the blood-air barrier to the lungs for their essential function of gas exchange after birth. The development of the surfactant and cortisol systems will also be discussed as these need to be mature before the lungs are able to take on their role of respiration following birth. It is clear that premature birth interrupts normal lung development so the effect of preterm birth on lung development will be examined and the respiratory consequences of very preterm birth will be briefly explored.

Gender differences in habitual activity in children with cystic fibrosis.

Aims: (1) To compare habitual activity levels in prepubescent and pubescent boys and girls with different degrees of CF lung disease severity and healthy controls. (2) To assess the relation between habitual activity levels and measures of fitness, lung function, nutrition, pancreatic status, and quality of life. Methods and Results: A total of 148 children (75 girls and 73 boys) with CF and matched controls were studied. Regardless of disease severity, there were no differences in habitual activity between prepubescent boys and girls with CF. Pubescent boys with CF were significantly more active than girls with the same degree of disease severity. There were no significant differences in habitual activity between prepubescent children with CF and controls. Pubescent children with mild CF were significantly more active than controls, but those with moderate to severe disease were less active than controls. The best correlates with habitual activity levels were anaerobic power, aerobic capacity, and quality of life. In children with moderate to severe disease, nutrition status correlated significantly with activity levels. The impact of pancreatic status on activity levels and other measures of fitness was most apparent in pubescent girls. Conclusion: Gender differences in habitual activity were evident only after the onset of puberty. The impact of pancreatic insufficiency on measures of fitness and habitual activity was greatest in pubescent females. The reason for this gender difference may be an interplay of genetic, hormonal, and societal factors and is the focus of a longitudinal study.

Using Index of Ventilation to Assess Response to Treatment for Acute Pulmonary Exacerbation in Children With Cystic Fibrosis

The use of alternative more sensitive measures has become a focus of research in CF. The utility of indexes of ventilation, Lung Clearance Index (LCI) and peak aerobic capacity (peak VO2), were studied as assessment tools in gauging response to intravenous (IV) therapy in acute pulmonary exacerbation, in comparison to the more commonly used index of forced expiratory volume in 1 sec (FEV1). The utility of a previously published clinical score was further explored.

Bioenergetic provision of energy for muscular activity

A complex series of metabolic pathways are present in human muscle that break down substrates from nutritional sources to produce energy for different types of muscular activity. However, depending on the activity in which an individual is engaged, the body will make use of different energy systems that have been adapted for the particular activity. More specifically, utilization of bioenergetic substrates depends on the type, intensity, and duration of the exercise. The aerobic oxidative system is used for longer duration activities of low to moderate intensity, the anaerobic glycolytic system is used for short to moderate duration activities of higher intensity, and the high energy phosphagen system is used for short duration activities of high intensity. The efficiency and effectiveness of these pathways can be enhanced through physical activity and training. It is these bioenergetic pathways that are the focus of this review.

Skeletal Muscle Metabolism in Cystic Fibrosis and Primary Ciliary Dyskinesia

Previous studies have reported differences in muscle function and metabolism between patients with cystic fibrosis (CF) and healthy controls (HC), but it is currently unknown whether these abnormalities are specific to CF or also seen in other airway diseases. In this study, we used magnetic resonance spectroscopy (MRS) during exercise to assess muscle metabolism in CF patients. Twenty patients with CF and 20 age, gender, and habitual activity-matched HCs and a respiratory disease comparison group with primary ciliary dyskinesia (PCD; n = 10) were studied. 31Phosphorus MRS (31P-MRS) was used to characterize muscle bioenergetic metabolism at rest and after high-, moderate-, and low-intensity exercise. CF patients exhibited lower resting ATP/phosphocreatine (PCr) ratio and significantly higher end-exercise pH values compared with both HC and PCD patients. Both CF and PCD patients demonstrated significantly slower PCr recovery time constants after high-intensity exercise. Our results suggest that not only there are specific abnormalities of muscle metabolism in CF patients but also there is a nonspecific impact of respiratory disease on muscle function.

Bacterial causes of empyema in children, Australia, 2007-2009

Most infections were caused by non–7-valent pneumococcal conjugate vaccine serotypes.

Childhood interstitial lung disease: A systematic review

Childhood interstitial lung disease (chILD) is a group of rare chronic and complex disorders of variable pathology. There has been no systematic review of published chILD research. This study aimed to describe chILD classification systems, epidemiology, morbidity, treatments, outcomes, and the impact of chILD on families and the burden on health services.

Lung clearance index in cystic fibrosis subjects treated for pulmonary exacerbations

Pulmonary exacerbations are important clinical events for cystic fibrosis (CF) patients. Studies assessing the ability of the lung clearance index (LCI) to detect treatment response for pulmonary exacerbations have yielded heterogeneous results. Here, we conduct a retrospective analysis of pooled LCI data to assess treatment with intravenous antibiotics for pulmonary exacerbations and to understand factors explaining the heterogeneous response. A systematic literature search was performed to identify prospective observational studies. Factors predicting the relative change in LCI and spirometry were evaluated while adjusting for within-study clustering. Six previously reported studies and one unpublished study, which included 176 pulmonary exacerbations in both paediatric and adult patients, were included. Overall, LCI significantly decreased by 0.40 units (95% CI −0.60– −0.19, p=0.004) or 2.5% following treatment. The relative change in LCI was significantly correlated with the relative change in forced expiratory volume in 1 s (FEV1), but results were discordant in 42.5% of subjects (80 out of 188). Higher (worse) baseline LCI was associated with a greater improvement in LCI (slope: −0.9%, 95% CI −1.0– −0.4%). LCI response to therapy for pulmonary exacerbations is heterogeneous in CF patients; the overall effect size is small and results are often discordant with FEV1. Lung clearance index response to therapy for pulmonary exacerbations is heterogeneous in cystic fibrosis patients http://ow.ly/Mnvtd

Does carbon dioxide retention during exercise predict a more rapid decline in FEV1 in cystic fibrosis

Background: Carbon dioxide (CO2) retention during exercise is uncommon in mild to moderate lung disease in cystic fibrosis (CF). The ability to deal with increased CO2 is dependent on the degree of airflow limitation and inherent CO2 sensitivity. CO2 retention (CO2R) can be defined as a rise in PETCO2 tension of ⩾5 mm Hg with exercise together with a failure to reduce PETCO2 tension after peak work by at least 3 mm Hg by the termination of exercise. Aim: To ascertain if carbon dioxide retention during exercise is associated with more rapid decline in lung function. Methods: Annual spirometric and exercise data from 58 children aged 11–15 years, with moderate CF lung disease between 1996 and 2002 were analysed. Results: The mean FEV1 at baseline for the two groups was similar; the CO2R group (n = 15) was 62% and the non-CO2 retention group (CO2NR) was 64% (n = 43). The decline in FEV1 after 12 months was −3.2% (SD 1.1) in the CO2R group and −2.3% (SD 0.9) in the CO2NR group. The decline after 24 months was −6.3% (SD 1.3) and −1.8% (SD 1.1) respectively. After 36 months, the decline in FEV1 was −5.3% (SD 1.2) and −2.6% (SD 1.1) respectively. The overall decline in lung function was 14.8% (SD 2.1) in the CO2R group and 6.7% (SD 1.8) in the CO2NR group. Using the primary outcome measure as a decline in FEV1 of >9%, final multivariate analysis showed that the relative risks for this model were (95% CIs in parentheses): ΔPETCO2 11.61 (3.41 to 24.12), peak V˙O2 1.23 (1.10 to 1.43), and initial FEV1 1.14 (1.02 to 1.28). Conclusion: Results show that the inability to defend carbon dioxide during exercise is associated with a more rapid decline in lung function.

Cystic fibrosis-related diabetes in children—gaps in the evidence?

As the life span of patients with cystic fibrosis has increased, so has the prevalence of cystic fibrosis-related diabetes mellitus. However, screening practices for cystic fibrosis-related diabetes mellitus vary widely, which affects accurate estimates of the health burden of this comorbidity. The management of prediabetes and hyperglycemia is an increasingly important aspect of care in patients with cystic fibrosis, but few studies have specifically addressed the management of cystic fibrosis-related diabetes mellitus. Previous studies support the use of insulin for the treatment of patients with this disorder, but the evidence for its use in patients with cystic fibrosis and impaired glucose tolerance is poor. Nutritional management is currently guided by dietary recommendations for individuals with cystic fibrosis, with little evidence specific to the dietary management of patients with cystic fibrosis-related diabetes mellitus. Additionally, microvascular complications have become more frequent as a result of the rise in life expectancy of these patients, yet to date no intervention studies have addressed prevention or management of diabetic complications in patients with cystic fibrosis. A strong evidence base is needed to guide the management of patients with cystic fibrosis-related diabetes mellitus and its complications.