Psychological interventions for asthma in children and adolescents.

BACKGROUND: Rates of asthma are high in children and adolescents, and young people with asthma generally report poorer health outcomes than those without asthma. Young people with asthma experience a range of challenges that may contribute to psychological distress. This is compounded by the social, psychological, and developmental challenges experienced by all people during this life stage. Psychological interventions (such as behavioural therapies or cognitive therapies) have the potential to reduce psychological distress and thus improve behavioural outcomes such as self-efficacy and medication adherence. In turn, this may reduce medical contacts and asthma attacks. OBJECTIVES: To determine the efficacy of psychological interventions for modifying health and behavioural outcomes in children with asthma, compared with usual treatment, treatment with no psychological component, or no treatment. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register (including CENTRAL, CRS, MEDLINE, Embase, PsycINFO, CINAHL EBSCO, AMED EBSCO), proceedings of major respiratory conferences, reference lists of included studies, and online clinical databases. The most recent search was conducted on 22 August 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing psychological interventions of any duration with usual care, active controls, or a waiting-list control in male and female children and adolescents (aged five to 18 years) with asthma. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. symptoms of anxiety and depression, 2. medical contacts, and 3. asthma attacks. Our secondary outcomes were 1. self-reported asthma symptoms, 2. medication use, 3. quality of life, and 4. adverse events/side effects. MAIN RESULTS: We included 24 studies (1639 participants) published between 1978 and 2021. Eleven studies were set in the USA, five in China, two in Sweden, three in Iran, and one each in the Netherlands, UK, and Germany. Participants' asthma severity ranged from mild to severe. Three studies included primary school-aged participants (five to 12 years), two included secondary school-aged participants (13 to 18 years), and 18 included both age groups, while one study was unclear on the age ranges. Durations of interventions ranged from three days to eight months. One intervention was conducted online and the rest were face-to-face. Meta-analysis was not possible due to clinical heterogeneity (interventions, populations, outcome tools and definitions, and length of follow-up). We tabulated and summarised the results narratively with reference to direction, magnitude, and certainty of effects. The certainty of the evidence was very low for all outcomes. A lack of information about scale metrics and minimal clinically important differences for the scales used to measure anxiety, depression, asthma symptoms, medication use, and quality of life made it difficult to judge clinical significance. Primary outcomes Four studies (327 participants) reported beneficial or mixed effects of psychological interventions versus controls for symptoms of anxiety, and one found little to no difference between groups (104 participants). Two studies (166 participants) that evaluated symptoms of depression both reported benefits of psychological interventions compared to controls. Three small studies (92 participants) reported a reduction in medical contacts, but two larger studies (544 participants) found little or no difference between groups in this outcome. Two studies (107 participants) found that the intervention had an important beneficial effect on number of asthma attacks, and one small study (22 participants) found little or no effect of the intervention for this outcome. Secondary outcomes Eleven studies (720 participants) assessed asthma symptoms; four (322 participants) reported beneficial effects of the intervention compared to control, five (257 participants) reported mixed or unclear findings, and two (131 participants) found little or no difference between groups. Eight studies (822 participants) reported a variety of medication use measures; six of these studies (670 participants) found a positive effect of the intervention versus control, and the other two (152 participants) found little or no difference between the groups. Across six studies (653 participants) reporting measures of quality of life, the largest three (522 participants) found little or no difference between the groups. Where findings were positive or mixed, there was evidence of selective reporting (2 studies, 131 participants). No studies provided data related to adverse effects. AUTHORS' CONCLUSIONS: Most studies that reported symptoms of anxiety, depression, asthma attacks, asthma symptoms, and medication use found a positive effect of psychological interventions versus control on at least one measure. However, some findings were mixed, it was difficult to judge clinical significance, and the evidence for all outcomes is very uncertain due to clinical heterogeneity, small sample sizes, incomplete reporting, and risk of bias. There is limited evidence to suggest that psychological interventions can reduce the need for medical contact or improve quality of life, and no studies reported adverse events. It was not possible to identify components of effective interventions and distinguish these from interventions showing no evidence of an effect due to substantial heterogeneity. Future investigations of evidence-based psychological techniques should consider standardising outcomes to support cross-comparison and better inform patient and policymaker decision-making.

'It gives me more freedom': Family perspectives on travelling with children on nocturnal ventilation.

BACKGROUND: Children with neuromuscular weakness or central hypoventilation often require nocturnal ventilation. Children with these conditions are living longer and the numbers of children affected are increasing. The challenges associated with managing ventilation at home have been documented; however, there has been limited investigation into accessing wider experiences such as travel. Air travel, in particular, may be considered challenging for children with these conditions because oxygen levels are lower in airplane cabins than at sea levels. OBJECTIVE: We sought to understand experiences of and attitudes towards travel amongst families of children using nocturnal ventilation for neuromuscular weakness or central hypoventilation. METHODS: Two semi-structured interviews were conducted amongst participants enrolled in a trial of a new pre-flight assessment of their tolerance of reduced oxygen levels during flight (known as a hypoxic challenge test). Children participating in the trial were aged 19 months to 18 years. Parents were interviewed and provided proxy views for younger children, and older children were encouraged to present their own views during these interviews. One interview was conducted immediately after the assessment, and a second 3 months later. Data were analysed utilising the framework approach to thematic analysis. RESULTS: Seventeen families participated in the first interview with 14 of these families completing the follow-up interview. Three further families participated in the follow-up interview only. Here, we report three themes relating to participant experience of travel and how this is impacted by their condition. The three themes and their sub-themes were (1) insight into children's lives: hospital attendances, gaining knowledge and confidence, and child as a person; (2) travelling with your child: planes, trains and automobiles, rules of air travel, and uncertainty; and (3) the meaning of travel: normalisation, connection to extended family, expanded experiences, and freedom and equality. CONCLUSIONS: This population of children and their families aspire to travel but face challenges from clinical and social barriers. It is essential that we further our understanding of the physiological, social and cultural aspects of their experience to facilitate their access to broadened life experiences.

Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA).

BACKGROUND: Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) Working Group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies. METHODS: COMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult and paediatric clinicians, pharmaceutical representatives, and health regulators from across Europe. Evidence included a systematic review of development, validity and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients' and carers' views about outcome measures. It was discussed using a modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria. RESULTS: Both adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z-scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire and Asthma Control Test or Childhood Asthma Control Test, while the adult COM set includes the Severe Asthma Questionnaire and Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately). CONCLUSIONS: This patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.

Modified hypoxic challenge testing in children needing nocturnal ventilation: An observational study.

BACKGROUND: Guidelines for air passengers with respiratory disease focus on primary lung pathology. Little evidence exists to guide professionals advising children needing ventilatory support because of neuromuscular or central hypoventilation conditions; these children might risk hypoxia and hypercapnia if unable to mount an adequate hyperventilation response. OBJECTIVE: This study assessed the response to low ambient oxygen using a modified hypoxic challenge test. In addition to measuring pulse oximetry and response to supplementary oxygen, we also measured transcutaneous carbon dioxide and response to ventilatory support. METHODS: Twenty children on nocturnal ventilatory support aged 1.6-18 years were recruited in a pragmatic sample from outpatient clinics; 10 with neuromuscular weakness and 10 with central hypoventilation. Participants underwent a two-stage, modified hypoxic challenge test; a conventional stage, where oxygen alone was titrated according to SpO2, and a new stage, where participants used their routine ventilatory support with oxygen titrated if needed. Participants were interviewed to understand their experiences of testing and of air travel. RESULTS: Thirteen participants needed supplemental oxygen during the conventional stage, but only two did when using ventilatory support. Transcutaneous carbon dioxide remained within normal range for all participants, on or off ventilatory support. Whilst some participants found testing challenging, participants generally reported both testing and air travel to be valuable. CONCLUSIONS: Evaluating response to patients' usual ventilation through "fitness-to-fly" assessment aids decision making when considering whether children who receive nocturnal ventilation can travel by air, since for some using a ventilator reduces or avoids the need for supplemental oxygen.

Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: a meta-analysis of 150 000 European children.

BACKGROUND: Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age. METHODS: We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4-15) years. RESULTS: Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: -0.09 (95% CI -0.14- -0.04) to -0.30 (95% CI -0.36- -0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98-2.22) to 6.30 (95% CI 5.64-7.04) and 1.25 (95% CI 1.18-1.32) to 1.55 (95% CI 1.47-1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma. CONCLUSIONS: Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections.

Interventions to improve adherence to pharmacological therapy for chronic obstructive pulmonary disease (COPD).

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic lung condition characterised by persistent respiratory symptoms and limited lung airflow, dyspnoea and recurrent exacerbations. Suboptimal therapy or non-adherence may result in limited effectiveness of pharmacological treatments and subsequently poor health outcomes. OBJECTIVES: To determine the efficacy and safety of interventions intended to improve adherence to single or combined pharmacological treatments compared with usual care or interventions that are not intended to improve adherence in people with COPD. SEARCH METHODS: We identified randomised controlled trials (RCTs) from the Cochrane Airways Trials Register, CENTRAL, MEDLINE and Embase (search date 1 May 2020). We also searched web-based clinical trial registers. SELECTION CRITERIA: RCTs included adults with COPD diagnosed by established criteria (e.g. Global Initiative for Obstructive Lung Disease). Interventions included change to pharmacological treatment regimens, adherence aids, education, behavioural or psychological interventions (e.g. cognitive behavioural therapy), communication or follow-up by a health professional (e.g. telephone, text message or face-to-face), multi-component interventions, and interventions to improve inhaler technique. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. Working in pairs, four review authors independently selected trials for inclusion, extracted data and assessed risk of bias. We assessed confidence in the evidence for each primary outcome using GRADE. Primary outcomes were adherence, quality of life and hospital service utilisation. Adherence measures included the Adherence among Patients with Chronic Disease questionnaire (APCD). Quality of life measures included the St George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT) and Clinical COPD Questionnaire (CCQ). MAIN RESULTS: We included 14 trials (2191 participants) in the analysis with follow-up ranging from six to 52 weeks. Age ranged from 54 to 75 years, and COPD severity ranged from mild to very severe. Trials were conducted in the USA, Spain, Germany, Japan, Jordan, Northern Ireland, Iran, South Korea, China and Belgium. Risk of bias was high due to lack of blinding. Evidence certainty was downgraded due to imprecision and small participant numbers. Single component interventions Six studies (55 to 212 participants) reported single component interventions including changes to pharmacological treatment (different roflumilast doses or different inhaler types), adherence aids (Bluetooth inhaler reminder device), educational (comprehensive verbal instruction), behavioural or psychological (motivational interview). Change in dose of roflumilast may result in little to no difference in adherence (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.22 to 1.99; studies = 1, participants = 55; low certainty). A Bluetooth inhaler reminder device did not improve adherence, but comprehensive verbal instruction from a health professional did improve mean adherence (prescription refills) (mean difference (MD) 1.00, 95% CI 0.46 to 1.54). Motivational interview improved mean adherence scores on the APCD scale (MD 22.22, 95% CI 8.42 to 36.02). Use of a single inhaler compared to two separate inhalers may have little to no impact on quality of life (SGRQ; MD 0.80, 95% CI -3.12 to 4.72; very low certainty). A Bluetooth inhaler monitoring device may provide a small improvement in quality of life on the CCQ (MD 0.40, 95% CI 0.07 to 0.73; very low certainty). Single inhaler use may have little to no impact on the number of people admitted to hospital compared to two separate inhalers (OR 1.47, 95% CI 0.75 to 2.90; very low certainty). Single component interventions may have little to no impact on the number of people expereincing adverse events (very low certainty evidence from studies of a change in pharmacotherapy or use of adherence aids). A change in pharmacotherapy may have little to no impact on exacerbations or deaths (very low certainty). Multi-component interventions Eight studies (30 to 734 participants) reported multi-component interventions including tailored care package that included adherence support as a key component or included inhaler technique as a component. A multi-component intervention may result in more people adhering to pharmacotherapy compared to control at 40.5 weeks (risk ratio (RR) 1.37, 95% CI 1.18 to 1.59; studies = 4, participants = 446; I2 = 0%; low certainty). There may be little to no impact on quality of life (SGRQ, Chronic Respiratory Disease Questionnaire, CAT) (studies = 3; low to very low certainty). Multi-component interventions may help to reduce the number of people admitted to hospital for any cause (OR 0.37, 95% CI 0.22 to 0.63; studies = 2, participants = 877; low certainty), or COPD-related hospitalisations (OR 0.15, 95% CI 0.07 to 0.34; studies = 2, participants = 220; moderate certainty). There may be a small benefit on people experiencing severe exacerbations. There may be little to no effect on adverse events, serious adverse events or deaths, but events were infrequently reported and were rare (low to very certainty). AUTHORS' CONCLUSIONS: Single component interventions (e.g. education or motivational interviewing provided by a health professional) can help to improve adherence to pharmacotherapy (low to very low certainty). There were slight improvements in quality of life with a Bluetooth inhaler device, but evidence is from one study and very low certainty. Change to pharmacotherapy (e.g. single inhaler instead of two, or different doses of roflumilast) has little impact on hospitalisations or exacerbations (very low certainty). There is no difference in people experiencing adverse events (all-cause or COPD-related), or deaths (very low certainty). Multi-component interventions may improve adherence with education, motivational or behavioural components delivered by health professionals (low certainty). There is little to no impact on quality of life (low to very low certainty). They may help reduce the number of people admitted to hospital overall (specifically pharmacist-led approaches) (low certainty), and fewer people may have COPD-related hospital admissions (moderately certainty). There may be a small reduction in people experiencing severe exacerbations, but evidence is from one study (low certainty). Limited evidence found no difference in people experiencing adverse events, serious adverse events or deaths (low to very low certainty). The evidence presented should be interpreted with caution. Larger studies with more intervention types, especially single interventions, are needed. It is unclear which specific COPD subgroups would benefit, therefore discussions between health professionals and patients may help to determine whether they will help to improve health outcomes.

Physical activity among children with asthma: Cross-sectional analysis in the UK millennium cohort.

BACKGROUND: Although beneficial for health and well-being, most children do not achieve recommended levels of physical activity. Evidence for children with asthma is mixed, with symptom severity rarely considered. This paper aimed to address this gap. METHODS: We analyzed cross-sectional associations between physical activity and parent-reported asthma symptoms and severity for 6497 UK Millennium Cohort Study 7-year-old participants (3321, [49%] girls). Primary outcomes were daily moderate-to-vigorous physical activity (MVPA, minutes) and proportion of children achieving recommended minimum daily levels of 60 minutes of MVPA. Daily steps, sedentary time, and total activity counts per minute (cpm) were recorded, as were parent-reported asthma symptoms, medications, and recent hospital admissions. Associations were investigated using quantile (continuous outcomes) and Poisson (binary outcomes) regression, adjusting for demographic, socioeconomic, health, and environmental factors. RESULTS: Neither asthma status nor severity was associated with MVPA; children recently hospitalized for asthma were less likely to achieve recommended daily MVPA (risk ratio [95% confidence interval [CI]]: 0.67 [0.44, 1.03]). Recent wheeze, current asthma, and severe asthma symptoms were associated with fewer sedentary hours (difference in medians [95% CI]: -0.18 [-0.27, -0.08]; -0.14 [-0.24, -0.05]; -0.15, [-0.28, -0.02], respectively) and hospital admission with lower total activity (-48 cpm [-68, -28]). CONCLUSION: Children with asthma are as physically active as their asthma-free counterparts, while those recently hospitalized for asthma are less active. Qualitative studies are needed to understand the perceptions of children and families about physical activity following hospital admission and to inform support and advice needed to maintain active lifestyles for children with asthma.

Change in FEV1 and Feno Measurements as Predictors of Future Asthma Outcomes in Children.

BACKGROUND: Repeated measurements of spirometry and fractional exhaled nitric oxide (Feno) are recommended as part of the management of childhood asthma, but the evidence base for such recommendations is small. We tested the hypothesis that reducing spirometric indices or increasing Feno will predict poor future asthma outcomes. METHODS: A one-stage individual patient data meta-analysis used data from seven randomized controlled trials in which Feno was used to guide asthma treatment; spirometric indices were also measured. Change in %FEV1 and % change in Feno between baseline and 3 months were related to having poor asthma control and to having an asthma exacerbation between 3 and 6 months after baseline. RESULTS: Data were available from 1,112 children (mean age, 12.6 years; mean %FEV1, 94%). A 10% reduction in %FEV1 between baseline and 3 months was associated with 28% increased odds for asthma exacerbation (95% CI, 3-58) and with 21% increased odds for having poor asthma control (95% CI, 0-45) 6 months after baseline. A 50% increase in Feno between baseline and 3 months was associated with 11% increase in odds for poor asthma control 6 months after baseline (95% CI, 0-16). Baseline Feno and %FEV1 were not related to asthma outcomes at 3 months. CONCLUSIONS: Repeated measurements of %FEV1 that are typically within the "normal" range add to clinical risk assessment of future asthma outcomes in children. The role of repeated Feno measurements is less certain because large changes were associated with small changes in outcome risk.

Interventions for autumn exacerbations of asthma in children.

BACKGROUND: Asthma exacerbations in school-aged children peak in autumn, shortly after children return to school following the summer holiday. This might reflect a combination of risk factors, including poor treatment adherence, increased allergen and viral exposure, and altered immune tolerance. Since this peak is predictable, interventions targeting modifiable risk factors might reduce exacerbation-associated morbidity and strain upon health resources. The peak occurs in September in the Northern Hemisphere and in February in the Southern Hemisphere. OBJECTIVES: To assess the effects of pharmacotherapy and behavioural interventions enacted in anticipation of school return during autumn that are designed to reduce asthma exacerbations in children during this period. SEARCH METHODS: We searched the Cochrane Airways Group Trials Register, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, reference lists of primary studies and existing reviews, and manufacturers' trial registries (Merck, Novartis and Ono Parmaceuticals). We searched databases from their inception to 1 December 2017, and imposed no restriction on language of publication. SELECTION CRITERIA: We included all randomised controlled trials comparing interventions aimed specifically at reducing autumn exacerbations with usual care, (no systematic change in management in preparation for school return). We included studies providing data on children aged 18 years or younger. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two review authors independently screened records identified by the search and then extracted data and assessed bias for trials meeting the inclusion criteria. A third review author checked for accuracy and mediated consensus on disagreements. The primary outcome was proportion of children experiencing one or more asthma exacerbations requiring hospitalisation or oral corticosteroids during the autumn period. MAIN RESULTS: Our searches returned 546 trials, of which five met our inclusion criteria. These studies randomised 14,252 children to receive either an intervention or usual care. All studies were conducted in the Northern Hemisphere. Three interventions used a leukotriene receptor antagonist, one used omalizumab or a boost of inhaled corticosteroids, and the largest study, (12,179 children), used a medication reminder letter. Whilst the risk of bias within individual studies was generally low, we downgraded the evidence quality due to imprecision associated with low participant numbers, poor consistency between studies, and indirect outcome ascertainment.A US study of 513 children with mild/severe asthma and allergic sensitisation was the only study to provide data for our primary outcome. In this study, the proportion of participants experiencing an exacerbation requiring oral corticosteroids or hospital admission in the 90 days after school return was significantly reduced to 11.3% in those receiving omalizumab compared to 21.0% in those receiving placebo (odds ratio 0.48, 95% confidence interval 0.25 to 0.92, moderate-quality evidence). The remaining studies used alternative exacerbation definitions. When data from two leukotriene receptor antagonist studies with comparable outcomes were combined in a random-effects model, there was no evidence of an effect upon exacerbations. There was no evidence that a seasonal medication reminder letter decreased unscheduled contacts for a respiratory diagnosis between September and December.Four studies recorded adverse events. There was no evidence that the proportion of participants experiencing at least one adverse event differed between intervention and usual care groups. Lack of data prevented planned subgroup and sensitivity analyses. AUTHORS' CONCLUSIONS: Seasonal omalizumab treatment from four to six weeks before school return might reduce autumn asthma exacerbations. We found no evidence that this strategy is associated with increased adverse effects other than injection site pain, but it is costly. There were no data upon which to judge the effect of this or other seasonal interventions on asthma control, quality of life, or asthma-related death. In future studies definitions of exacerbations should be provided, and standardised where possible. To investigate possible differential effects according to subgroup, participants in future trials should be well characterised with respect to baseline asthma severity and exacerbation history in addition to age and gender.

Managing problematic severe asthma: beyond the guidelines.

This review discusses issues related to managing problematic severe asthma in children and young people. A small minority of children have genuinely severe asthma symptoms which are difficult to control. Children with genuinely severe asthma need investigations and treatments beyond those described within conventional guidelines. However, the majority of children with poor symptom control despite high-intensity treatment achieve improvement in their asthma control once attention has been paid to the basics of asthma management. Basic asthma management requires optimisation of inhaler technique and treatment adherence, avoidance of environmental triggers and self-management education. It is also important that clinicians recognise risk factors that predispose patients to asthma exacerbations and potentially life-threatening attacks. These correctable issues need to be tackled in partnership with children and young people and their families. This requires a coordinated approach between professionals across healthcare settings. Establishing appropriate infrastructure for coordinated asthma care benefits not only those with problematic severe asthma, but also the wider asthma population as similar correctable issues exist for children with asthma of all severities. Investigation and management of genuine severe asthma requires specialist multidisciplinary expertise and a systematic approach to characterising patients' asthma phenotypes and delivering individualised care. While inhaled corticosteroids continue to play a leading role in asthma therapy, new treatments on the horizon might further support phenotype-specific therapy.

Maternal body mass index: Relation with infant respiratory symptoms and infections.

BACKGROUND: Maternal obesity is increasingly prevalent in many westernized countries. Many studies report associations between maternal obesity and childhood wheeze or asthma but few have considered maternal obesity in relation to respiratory infections or symptoms other than wheeze during infancy. This study assesses the relationship between maternal BMI and reported wheeze, cough and respiratory infections during the first year of life. METHODS: In 2799 mother-child pairs, we examined the relations between maternal pre-pregnancy BMI and pregnancy weight gain and reported offspring wheeze, prolonged cough, lower respiratory tract infection, croup, and ear infection before age 1 year, along with reported diarrhea or vomiting. Maternally reported paternal BMI was included in the models as a proxy for unmeasured confounding by shared familial factors. RESULTS: Higher maternal BMI was associated with increased risks of offspring wheeze, prolonged cough and lower respiratory tract infection (relative risks (95%CI) per 5 kg/m2 1.09 (1.05-1.13), 1.09 (1.03-1.14), and 1.13 (1.07-1.20), respectively). These associations remained after adjusting for maternally reported paternal BMI. No associations were found with croup, ear infection, or diarrhea or vomiting. Pregnancy weight gain was not associated with any of the offspring symptoms or illnesses. DISCUSSION: Higher maternal BMI is associated with increased risk of wheeze, cough, and maternally reported lower respiratory tract infection in infancy. These associations were independent of maternally reported paternal BMI. These observations might be explained by intrauterine effects of maternal obesity upon respiratory or immune development.

Ciprofloxacin during upper respiratory tract infections to reduce Pseudomonas aeruginosa infection in paediatric cystic fibrosis: a pilot study.

OBJECTIVES: Acute viral respiratory illnesses are associated with acquisition of Pseudomonas aeruginosa infection in cystic fibrosis (CF) patients. This study aimed to pilot a protocol for a randomized controlled trial to determine whether oral antipseudomonal antibiotics used at the onset of such episodes might delay onset of infection with this organism. METHODS: A total of 41 children with CF aged 2-14 years, without chronic Pseudomonas infection, were randomized to receive ciprofloxacin (n = 28) or placebo (n = 13) at the onset of acute viral respiratory infections on an intention to treat basis, during a study period of up to 32 months. RESULTS: There were no unexpected adverse events believed related to the use of the study medication. The rate of withdrawal from the study was low (approximately 7%) and did not differ between groups. Randomization was effective and acceptable to participants. Primary and secondary outcome measures all favoured active treatment, but there were no significant between group differences. The median rate of Pseudomonas isolates was 0/patient/year (interquartile range 0-0.38) in both the active and placebo groups. Kaplan-Meier survival curves showed no significant difference in time to first Pseudomonas isolate between groups. CONCLUSIONS: This study demonstrated the clinical feasibility of using oral ciprofloxacin in CF patients at times of viral infection. Within this sample size, no significant association was found between active treatment and decreased growth of Pseudomonas in follow-up microbiological samples. A definitive study would require at least 320 children to demonstrate significant differences in the rate of pseudomonal isolates.

Nutritional outcomes in cystic fibrosis - are we doing enough?

Although outcome data for individuals with cystic fibrosis (CF) have shown consistent improvements throughout the twentieth century, more recent national registry data suggests that outcomes have reached a plateau. Median values for nutritional outcomes in CF currently cluster around the fiftieth centile for the normal population. These data suggest that up to half of CF patients have sub-optimal body mass index (BMI) which might have a significant adverse impact on their respiratory status. BMI might be underestimating the extent to which more important lean body mass might also be reduced. Nutritional decline is a particular problem during adolescence and commonly persists into early adult life. Current treatment strategies to optimize nutrition include the use of high energy diets, proton pump inhibitors and optimal use of enzyme preparations including higher strength preparations to decrease pill burden. Whilst these are all of potential benefit, poor adherence to nutritional care recommendations is probably the greatest impediment to future health improvement. More effective strategies to impact on treatment adherence are needed.

Respiratory consequences of late preterm birth.

In developed countries most preterm births occur between 34 and 37 weeks' gestation. Deliveries during this 'late preterm' period are increasing and, since even mild prematurity is now recognised to be associated with adverse health outcomes, this presents healthcare challenges. Respiratory problems associated with late preterm birth include neonatal respiratory distress, severe RSV infection and childhood wheezing. Late preterm birth prematurely interrupts in utero lung development and is associated with maternal and early life factors which adversely affect the developing respiratory system. This review considers 1) mechanisms underlying the association between late preterm birth and impaired respiratory development, 2) respiratory morbidity associated with late preterm birth, particularly long-term outcomes, and 3) interventions which might protect respiratory development by addressing risk factors affecting the late preterm population, including maternal smoking, early life growth restriction and vulnerability to viral infection.

Prenatal development is linked to bronchial reactivity: epidemiological and animal model evidence.

Chronic cardiorespiratory disease is associated with low birthweight suggesting the importance of the developmental environment. Prenatal factors affecting fetal growth are believed important, but the underlying mechanisms are unknown. The influence of developmental programming on bronchial hyperreactivity is investigated in an animal model and evidence for comparable associations is sought in humans. Pregnant Wistar rats were fed either control or protein-restricted diets throughout pregnancy. Bronchoconstrictor responses were recorded from offspring bronchial segments. Morphometric analysis of paraffin-embedded lung sections was conducted. In a human mother-child cohort ultrasound measurements of fetal growth were related to bronchial hyperreactivity, measured at age six years using methacholine. Protein-restricted rats' offspring demonstrated greater bronchoconstriction than controls. Airway structure was not altered. Children with lesser abdominal circumference growth during 11-19 weeks' gestation had greater bronchial hyperreactivity than those with more rapid abdominal growth. Imbalanced maternal nutrition during pregnancy results in offspring bronchial hyperreactivity. Prenatal environmental influences might play a comparable role in humans.

Preterm birth, infant weight gain, and childhood asthma risk: a meta-analysis of 147,000 European children.

BACKGROUND: Preterm birth, low birth weight, and infant catch-up growth seem associated with an increased risk of respiratory diseases in later life, but individual studies showed conflicting results. OBJECTIVES: We performed an individual participant data meta-analysis for 147,252 children of 31 birth cohort studies to determine the associations of birth and infant growth characteristics with the risks of preschool wheezing (1-4 years) and school-age asthma (5-10 years). METHODS: First, we performed an adjusted 1-stage random-effect meta-analysis to assess the combined associations of gestational age, birth weight, and infant weight gain with childhood asthma. Second, we performed an adjusted 2-stage random-effect meta-analysis to assess the associations of preterm birth (gestational age <37 weeks) and low birth weight (<2500 g) with childhood asthma outcomes. RESULTS: Younger gestational age at birth and higher infant weight gain were independently associated with higher risks of preschool wheezing and school-age asthma (P < .05). The inverse associations of birth weight with childhood asthma were explained by gestational age at birth. Compared with term-born children with normal infant weight gain, we observed the highest risks of school-age asthma in children born preterm with high infant weight gain (odds ratio [OR], 4.47; 95% CI, 2.58-7.76). Preterm birth was positively associated with an increased risk of preschool wheezing (pooled odds ratio [pOR], 1.34; 95% CI, 1.25-1.43) and school-age asthma (pOR, 1.40; 95% CI, 1.18-1.67) independent of birth weight. Weaker effect estimates were observed for the associations of low birth weight adjusted for gestational age at birth with preschool wheezing (pOR, 1.10; 95% CI, 1.00-1.21) and school-age asthma (pOR, 1.13; 95% CI, 1.01-1.27). CONCLUSION: Younger gestational age at birth and higher infant weight gain were associated with childhood asthma outcomes. The associations of lower birth weight with childhood asthma were largely explained by gestational age at birth.