Sex and the lung: Observations, hypotheses, and future directions.

Sex-related differences in a variety of lung diseases in infants and young children are reviewed, including respiratory distress syndrome, and chronic lung disease of prematurity, lower respiratory tract illnesses and wheezing, asthma, diffuse, and interstitial lung diseases, and cystic fibrosis. Differences in anatomy and physiology, such as airway size, airway muscle bulk, airway reactivity, airway tone, and cough reflexes may explain much of these sex differences. Better understanding of sex-related lung differences could help personalize respiratory treatment.

Children with chronic cough: when is watchful waiting appropriate? development of likelihood ratios for assessing children with chronic cough.

BACKGROUND: Chronic cough is associated with poor quality of life and may signify a serious underlying disease. Differentiating nonspecific cough (when watchful waiting can be safely undertaken) from specific cough (treatment and further investigations are beneficial) would be clinically useful. In 326 children, we aimed to (1) determine how well cough pointers (used in guidelines) differentiate specific from nonspecific cough and (2) describe the clinical profile of children whose cough resolved without medications (spontaneous resolution). METHODS: A dataset from a multicenter study involving children newly referred for chronic cough (median duration, 3-4 months) was used to determine the sensitivity, specificity, predictive values, and likelihood ratios (LRs) of cough pointers (symptoms, signs, and simple investigations [chest radiography, spirometry]) recommended in guidelines. RESULTS: The pretest probability of specific cough was 88%. The absence of false-positive results meant that most pointers had strongly positive LRs. The most sensitive pointer (wet cough) had a positive LR of 26.2 (95% CI, 3.8-181.5). Although the absence of other individual pointers did not change the pretest probability much (negative LR close to 1), the absence of all pointers had a strongly negative LR of 0 (95% CI, 0-0.03). Children in the resolved spontaneously group were significantly more likely to be older, to be non-Indigenous, and to have a dry cough and a normal chest radiograph. CONCLUSIONS: Children with chronic dry cough without any cough pointers can be safely managed using the watchful waiting approach. The high pretest probability and high positive LRs of cough pointers support the use of individual cough pointers to identify high risk of specific cough in pediatric chronic cough guidelines. TRIAL REGISTRY: Australian New Zealand Clinical Trials Registry; No.: 12607000526471; URL: www.anzctr.org.au.

A cough algorithm for chronic cough in children: a multicenter, randomized controlled study.

OBJECTIVES: The goals of this study were to: (1) determine if management according to a standardized clinical management pathway/algorithm (compared with usual treatment) improves clinical outcomes by 6 weeks; and (2) assess the reliability and validity of a standardized clinical management pathway for chronic cough in children. METHODS: A total of 272 children (mean ± SD age: 4.5 ± 3.7 years) were enrolled in a pragmatic, multicenter, randomized controlled trial in 5 Australian centers. Children were randomly allocated to 1 of 2 arms: (1) early review and use of cough algorithm ("early-arm"); or (2) usual care until review and use of cough algorithm ("delayed-arm"). The primary outcomes were proportion of children whose cough resolved and cough-specific quality of life scores at week 6. Secondary measures included cough duration postrandomization and the algorithm's reliability, validity, and feasibility. RESULTS: Cough resolution (at week 6) was significantly more likely in the early-arm group compared with the delayed-arm group (absolute risk reduction: 24.7% [95% confidence interval: 13-35]). The difference between cough-specific quality of life scores at week 6 compared with baseline was significantly better in the early-arm group (mean difference between groups: 0.6 [95% confidence interval: 0.29-1.0]). Duration of cough postrandomization was significantly shorter in the early-arm group than in the delayed-arm group (P = .001). The cough algorithm was reliable (κ = 1 in key steps). Feasibility was demonstrated by the algorithm's validity (93%-100%) and efficacy (99.6%). Eighty-five percent of children had etiologies easily diagnosed in primary care. CONCLUSIONS: Management of children with chronic cough, in accordance with a standardized algorithm, improves clinical outcomes irrespective of when it is implemented. Further testing of this standardized clinical algorithm in different settings is recommended.

Lifecourse childhood adiposity trajectories associated with adolescent insulin resistance.

OBJECTIVE: In light of the obesity epidemic, we aimed to characterize novel childhood adiposity trajectories from birth to age 14 years and to determine their relation to adolescent insulin resistance. RESEARCH DESIGN AND METHODS: A total of 1,197 Australian children with cardiovascular/metabolic profiling at age 14 years were studied serially from birth to age 14 years. Semiparametric mixture modeling was applied to anthropometric data over eight time points to generate adiposity trajectories of z scores (weight-for-height and BMI). Fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were compared at age 14 years between adiposity trajectories. RESULTS: Seven adiposity trajectories were identified. Three (two rising and one chronic high adiposity) trajectories comprised 32% of the population and were associated with significantly higher fasting insulin and HOMA-IR compared with a reference trajectory group (with longitudinal adiposity z scores of approximately zero). There was a significant sex by trajectory group interaction (P < 0.001). Girls within a rising trajectory from low to moderate adiposity did not show increased insulin resistance. Maternal obesity, excessive weight gain during pregnancy, and gestational diabetes were more prevalent in the chronic high adiposity trajectory. CONCLUSIONS: A range of childhood adiposity trajectories exist. The greatest insulin resistance at age 14 years is seen in those with increasing trajectories regardless of birth weight and in high birth weight infants whose adiposity remains high. Public health professionals should urgently target both excessive weight gain in early childhood across all birth weights and maternal obesity and excessive weight gain during pregnancy.

Differential relationships between anthropometry measures and cardiovascular risk factors in boys and girls.

OBJECTIVES: The aim of the study was to compare commonly used anthropometry for cardiovascular risk factors in 14-year-olds. METHODS: A total of 1 149 children of an Australian pregnancy (Raine) cohort with recruitment 1989-1991 were assessed for anthropometry and fasting lipids, insulin, and blood pressure. RESULTS: There were significant distinctions in the associations between anthropometry and groups of cardiovascular risk factors. These distinctions differed by gender. Insulin resistance, triglycerides, C-reactive protein levels, low density lipoprotein (LDH)/high density lipoprotein (HDL) and total/HDL cholesterol ratios had the strongest association with waist, waist/height ratio and body mass index. By contrast, in boys, height was the strongest independent predictor (in a negative direction) of total and LDL-cholesterol. Blood pressure and uric acid was most strongly correlated with body weight and height (heavier and taller boys). Taller male adolescents had highest blood pressures and lowest cholesterol levels. CONCLUSIONS: No single adolescent anthropometric measure best predicted all cardiovascular risk factors. Each measure showed distinct relationships with specific groups of risk factors. Contrasting associations may reflect different pathogenesis by which gender, puberty, and adiposity affect metabolic risk. No single anthropometric measurement in childhood would appear to be superior or sufficient when investigating the developmental origins of cardiovascular health and related metabolic disease.

Driving change in rural workforce planning: the medical schools outcomes database.

The Medical Schools Outcomes Database (MSOD) is an ongoing longitudinal tracking project ofmedical students from all medical schools in Australia and New Zealand. It was established in 2005 to track the career trajectories of medical students and will directly help develop models of workforce flow, particularly with respect to rural and remote shortages. This paper briefly outlines the MSOD project and reports on key methodological factors in tracking medical students. Finally, the potential impact of the MSOD on understanding changes in rural practice intentions is illustrated using data from the 2005 pilot cohort (n = 112). Rural placements were associated with a shift towards rural practice intentions, while those who intended to practice rurally at both the start and end of medical school tended to be older and interested in a generalist career. Continuing work will track these and future students as they progress through the workforce, as well as exploring issues such as the career trajectories of international fee-paying students, workforce succession planning, and the evaluation of medical education initiatives.

Chronic suppurative lung disease and bronchiectasis in children and adults in Australia and New Zealand.

Consensus recommendations for managing chronic suppurative lung disease (CSLD) and bronchiectasis, based on systematic reviews, were developed for Australian and New Zealand children and adults during a multidisciplinary workshop. The diagnosis of bronchiectasis requires a high-resolution computed tomography scan of the chest. People with symptoms of bronchiectasis, but non-diagnostic scans, have CSLD, which may progress to radiological bronchiectasis. CSLD/bronchiectasis is suspected when chronic wet cough persists beyond 8 weeks. Initial assessment requires specialist expertise. Specialist referral is also required for children who have either two or more episodes of chronic (> 4 weeks) wet cough per year that respond to antibiotics, or chest radiographic abnormalities persisting for at least 6 weeks after appropriate therapy. Intensive treatment seeks to improve symptom control, reduce frequency of acute pulmonary exacerbations, preserve lung function, and maintain a good quality of life. Antibiotic selection for acute infective episodes is based on results of lower airway culture, local antibiotic susceptibility patterns, clinical severity and patient tolerance. Patients whose condition does not respond promptly or adequately to oral antibiotics are hospitalised for more intensive treatments, including intravenous antibiotics. Ongoing treatment requires regular and coordinated primary health care and specialist review, including monitoring for complications and comorbidities. Chest physiotherapy and regular exercise should be encouraged, nutrition optimised, environmental pollutants (including tobacco smoke) avoided, and vaccines administered according to national immunisation schedules. Individualised long-term use of oral or nebulised antibiotics, corticosteroids, bronchodilators and mucoactive agents may provide a benefit, but are not recommended routinely.

Impact of structured education and self management on rural asthma outcomes.

BACKGROUND: This study trialled the outcome for asthma patients of a brief, nurse led, patient education session with general practice review of an Asthma Action Plan. METHODS: Prospective cohort with before-after measures conducted in six rural general practices. Outcome measures were changes over 12 months in self reported asthma control, quality of life, device use, and unscheduled general practice and emergency department visits for asthma exacerbation. RESULTS: Eighty-three patients participated. Mean asthma control score decreased but did not reach statistical significance (p=0.124). Quality of life improved for adults (Wilcoxon rank signed test for two related samples p<0.001). The proportion of patients who had one or more unscheduled visits to their general practitioner over 12 months decreased from 23% to 13% (p=0.178) and emergency department presentations decreased from 9% to 4% (p=0.102). DISCUSSION: Structured general practice based education appears to be an effective preventive health care program, with the potential to reduce expensive unscheduled use of health services.

CICADA: Cough in Children and Adults: Diagnosis and Assessment. Australian cough guidelines summary statement.

Cough is a common and distressing symptom that results in significant health care costs from medical consultations and medication use. Cough is a reflex activity with elements of voluntary control that forms part of the somatosensory system involving visceral sensation, a reflex motor response and associated behavioural responses. At the initial assessment for chronic cough, the clinician should elicit any alarm symptoms that might indicate a serious underlying disease and identify whether there is a specific disease present that is associated with chronic cough. If the examination, chest x-ray and spirometry are normal, the most common diagnoses in ADULTS are asthma, rhinitis or gastro-oesophageal reflux disease (GORD). The most common diagnoses in CHILDREN are asthma and protracted bronchitis. Management of chronic cough involves addressing the common issues of environmental exposures and patient or parental concerns, then instituting specific therapy. In ADULTS, conditions that are associated with removable causes or respond well to specific treatment include protracted bacterial bronchitis, angiotensin-converting enzyme inhibitor use, asthma, GORD, obstructive sleep apnoea and eosinophilic bronchitis. In CHILDREN, diagnoses that are associated with removable causes or respond well to treatment are exposure to environmental tobacco smoke, protracted bronchitis, asthma, motor tic, habit and psychogenic cough. In ADULTS, refractory cough that persists after therapy is managed by empirical inhaled corticosteroid therapy and speech pathology techniques.

In utero smoke exposure and role of maternal and infant glutathione s-transferase genes on airway responsiveness and lung function in infancy.

RATIONALE: Xenobiotics in the maternal circulation are capable of crossing the placental barrier so a reduction in the mother and fetus's detoxification ability due to genetic variation in the glutathione S-transferases (GSTs) could expose the fetus to higher levels of toxins. OBJECTIVES: To investigate the interactive effects of maternal smoking during pregnancy with maternal and infant GST genotypes on airway responsiveness (AR) and lung function in infancy. METHODS: GSTT1, GSTP1 and GSTM1 were genotyped in infants and mothers, in utero smoke exposure was evaluated by questionnaire, AR was assessed by histamine challenge and Vmax(FRC) was measured using the rapid thoracoabdominal compression technique. We investigated the interactive effects of maternal smoking during pregnancy with maternal and infant GST genes on AR and lung function at 1, 6, and 12 months and longitudinally throughout the first year. MEASUREMENTS AND MAIN RESULTS: Infant and/or maternal GSTT1 nonnull was associated with reduced AR at 12 months and throughout the first year and increased Vmax(FRC) at 6 months. Maternal GSTP1 Val/Val or Ile/Val was associated with increased Vmax(FRC) at 6 months. In infants exposed to in utero smoke, infant and/or maternal GSTT1 nonnull was associated with reduced AR at 1 month and throughout the first year and increased Vmax(FRC) throughout the first year. Maternal GSTP1 Val/Val or Ile/Val was associated with increased Vmax(FRC) at 6 months. CONCLUSIONS: GST genes may be especially important during fetal development as they may modify, through proficient detoxification, the effects of in utero maternal smoke exposure on AR and lung function in infants.

The long-term effects of breastfeeding on child and adolescent mental health: a pregnancy cohort study followed for 14 years.

OBJECTIVES: To determine whether there was an independent effect of breastfeeding on child and adolescent mental health. STUDY DESIGN: The Western Australian Pregnancy Cohort (Raine) Study recruited 2900 pregnant women and followed the live births for 14 years. Mental health status was assessed by the Child Behaviour Checklist (CBCL) at 2, 6, 8, 10, and 14 years. Maternal pregnancy, postnatal, and infant factors were tested in multivariable random effects models and generalized estimating equations to examine the effects of breastfeeding duration on mental health morbidity. RESULTS: Breastfeeding for less than 6 months compared with 6 months or longer was an independent predictor of mental health problems through childhood and into adolescence. This relationship was supported by the random effects models (increase in total CBCL score: 1.45; 95% confidence interval 0.59, 2.30) and generalized estimating equation models (odds ratio for CBCL morbidity: 1.33; 95% confidence interval 1.09, 1.62) showing increased behavioral problems with shorter breastfeeding duration. CONCLUSION: A shorter duration of breastfeeding may be a predictor of adverse mental health outcomes throughout the developmental trajectory of childhood and early adolescence.

Pediatric respiratory medicine--an international perspective.

Although Pediatric Respiratory Medicine as a subspecialty has a long tradition and is well established in some countries, there is a wide variation across different regions of the world with regard to e.g. recognition of the discipline, training requirements, training facilities and clinical needs. This review summarizes the situation in North America (US and Canada), South America, Asia, Australia, Israel and Europe with the aim to highlight commonalities and differences and, ultimately, to further support continuous development of paediatric Respiratory Medicine Worldwide.

Synergy between adiposity, insulin resistance, metabolic risk factors, and inflammation in adolescents.

OBJECTIVE: The purpose of this study was to investigate relationships between inflammatory markers and components of a metabolic syndrome cluster in adolescents. RESEARCH DESIGN AND METHODS: This was a cross-sectional analysis of an Australian childhood cohort (n = 1,377) aged 14 years. Cluster analysis defined a "high-risk" group similar to adults with metabolic syndrome. Relevant measures were anthropometry, fasting insulin, glucose, lipids, inflammatory markers, liver function, and blood pressure. RESULTS: Of the children, 29% fell into a high-risk metabolic cluster group compared with 2% by a pediatric metabolic syndrome definition. Relative to the "low-risk" cluster, they had higher BMI (95% CI 19.5-19.8 vs. 24.5-25.4), waist circumference (centimeters) (95% CI 71.0-71.8 vs. 83.4-85.8), insulin (units per liter) (95% CI 1.7-1.8 vs. 3.5-3.9), homeostasis model assessment (95% CI 1.7-1.8 vs. 3.5-3.9), systolic blood pressure (millimeters of mercury) (95% CI 110.8-112.1 vs. 116.7-118.9), and triglycerides (millimoles per liter) (95% CI 0.78-0.80 vs. 1.25-1.35) and lower HDL cholesterol (millimoles per liter) (95% CI 1.44-1.48 vs. 1.20-1.26). Inflammatory and liver function markers were higher in the high-risk group: C-reactive protein (CRP) (P < 0.001), uric acid (P < 0.001), alanine aminotransferase (ALT) (P < 0.001), and gamma-glutamyl transferase (GGT) (P < 0.001). The highest CRP, GGT, and ALT levels were restricted to overweight children in the high-risk group. CONCLUSIONS: Cluster analysis revealed a strikingly high proportion of 14 year olds at risk of cardiovascular disease-related metabolic disorders. Adiposity and the metabolic syndrome cluster are synergistic in the pathogenesis of inflammation. Systemic and liver inflammation in the high-risk cluster is likely to predict diabetes, cardiovascular disease, and nonalcoholic fatty liver disease.

Childhood asthma and increased airway responsiveness: a relationship that begins in infancy.

RATIONALE: Asthma is associated with increased airway responsiveness (AR), but the age when this relationship becomes established is not clear. The present study tested the hypothesis that the association between increased AR and asthma is established after 1 month of age. OBJECTIVES: To relate AR in infancy to asthma in childhood. METHODS: As part of a birth cohort study, AR was determined at 1 (early infancy), 6 (mid-infancy), and 12 months of age (late infancy). At 11 years of age (childhood), AR and the presence of asthma symptoms were determined. MEASUREMENTS AND MAIN RESULTS: Of the 253 study subjects enrolled, AR was determined in 202 in early infancy, 174 in mid-infancy, 147 in late infancy, and 176 in childhood. Increased AR in late infancy, but not in early or mid-infancy, was associated with increased wheeze at 11 years of age (P = 0.016). Increased AR in infancy persisted into childhood in association with male gender, early respiratory illness, and maternal smoking and asthma. Among the 116 subjects assessed in late infancy and childhood, recent wheeze was present in 35% of children with increased AR at both ages, 13% with increased AR in childhood only, 12% for those with increased AR in late infancy only, and 0% for those who did not have increased AR at either age (P = 0.023); the proportions of children with diagnosed asthma in the corresponding groups were 27, 20, 12, and 0% (P = 0.038). CONCLUSIONS: The association between increased infantile AR and childhood asthma emerges at the end of the first year of life.

Infants with chronic neonatal lung disease: recommendations for the use of home oxygen therapy.

Chronic neonatal lung disease (CNLD) is defined as a supplemental oxygen requirement beyond 36 weeks' postmenstrual age, with more severely affected infants requiring oxygen beyond a full-term-equivalent age. Low-flow supplemental oxygen facilitates discharge from hospital of infants with CNLD who develop hypoxia in air. There is a lack of data on the most appropriate minimum mean target oxygen saturation (Spo(2)) level. Reflecting a variety of clinical practices and infant comorbidities (frequency of oxygen desaturation, presence of pulmonary hypertension, retinopathy of prematurity, and adequacy of growth), the minimum mean target range for Spo(2) during overnight oximetry should be 93%-95%. The effect of supplemental oxygen on carbon dioxide retention should be considered before deciding on an oxygen flow. Most infants with CNLD are not ready for discharge until their supplemental oxygen requirement is < or = 0.5 litres per minute delivered through a nasal cannula. The safety of short-term disconnection from supplemental oxygen should be assessed before discharge. Assessment of oxygenation during sleep with continuous overnight oximetry or polysomnography is recommended when weaning infants from supplemental oxygen. Discontinuation of oxygen therapy is based on clinical assessments and documentation of adequate oxygenation in room air. There is limited objective evidence on which to base recommendations.

Tobacco smoke exposure and tracking of lung function into adult life.

Maternal smoking during pregnancy leads to abnormal lung function in infancy that tracks through to later childhood and continues into adult life. This is associated with transient wheezing illnesses through early childhood. Both social and physiological factors are likely to predispose those exposed to passive smoke to become active smokers. Adult smokers demonstrate an increased decline of lung function with age. The effects of passive smoke exposure vary with genetic factors, gender, race and exposure to other pollutants. Exposure to environmental tobacco smoke and subsequent active smoking both aggravate symptoms and have a negative effect on lung function in those with asthma.