Diffuse bronchiectasis of genetic origin

Bronchiectasis is a significant cause of morbidity and mortality. It is the end point of a pathological process. We should be aiming to identify at risk patients before they develop bronchiectasis and treat them aggressively to prevent disease progression. With improved social conditions and health care, infective causes of bronchiectasis have diminished in the developed world, and genetic causes are therefore relatively more common. The underlying cause of bronchiectasis should always be sought and redressed, for example as discoveries of innate immune defects are made. ‘Idiopathic bronchiectasis’ should be a diagnosis of last resort. This chapter reviews potential genetic causes of bronchiectasis and suggests a plan for investigating the underlying aetiology. Management is discussed but it is important to note that suggested treatment strategies are often extrapolated from evidence in bronchiectasis associated with cystic fibrosis; this is likely to be inappropriate in diseases of differing pathophysiology. Rare lung diseases need to be moved out of the ‘orphan’ category by instigating multi-centre, multi-national clinical trials and producing disease specific evidence based guidelines

Interventions for autumn exacerbations of asthma in children

The objectives are as follows: To assess the effects of pharmacotherapy and behavioural interventions enacted in the lead-up to the school return during autumn which are designed to reduce asthma exacerbations in school-aged children during this period

Psychological interventions for asthma in children and adolescents

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: Main objectives To determine the efficacy of psychological interventions in modifying health and behavioural outcomes in children with asthma, compared with usual treatment. Secondary objectives To compare efficacy of different types of psychological interventions for children with asthma. To assess the comparative efficacy of individual and group formats of psychological therapy for children with asthma

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

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

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

Birth data accessibility via primary care health records to classify health status in a multi-ethnic population of children: an observational study

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In utero exposure to 25-hydroxyvitamin D and risk of childhood asthma, wheeze, and respiratory tract infections: A meta-analysis of birth cohort studies

BACKGROUND: Studies of the associations between in utero 25-hydroxyvitamin D (25[OH]D) exposure and risk of childhood asthma, wheeze, and respiratory tract infections are inconsistent and inconclusive. OBJECTIVES: We sought to assess associations between 25(OH)D levels in cord blood or maternal venous blood and risk of offspring's asthma, wheeze, and respiratory tract infections. METHODS: Data were derived from PubMed, Embase, Google Scholar, references from relevant articles, and de novo results from published studies until December 2015. A random-effects meta-analysis was conducted among 16 birth cohort studies. RESULTS: Comparing the highest with the lowest category of 25(OH)D levels, the pooled odds ratios were 0.84 (95% CI, 0.70-1.01; P = .064) for asthma, 0.77 (95% CI, 0.58-1.03; P = .083) for wheeze, and 0.85 (95% CI, 0.66-1.09; P = .187) for respiratory tract infections. The observed inverse association for wheeze was more pronounced and became statistically significant in the studies that measured 25(OH)D levels in cord blood (0.43; 95% CI, 0.29-0.62; P < .001). CONCLUSIONS: Accumulated evidence generated from this meta-analysis suggests that increased in utero exposure to 25(OH)D is inversely associated with the risk of asthma and wheeze during childhood. These findings are in keeping with the results of 2 recently published randomized clinical trials of vitamin D supplementation during pregnancy

Validation of novel wheeze phenotypes using longitudinal airway function and atopic sensitization data in the first 6 years of life: evidence from the Southampton Women's survey.

BACKGROUND: In 1995 the Tucson Children's Respiratory Study (TCRS) identified clinically distinct phenotypes amongst early wheezers; the Avon Longitudinal Study of Parents And Children (ALSPAC) has recently re-examined these. OBJECTIVES: To validate statistically derived ALSPAC phenotypes in the Southampton Women's Survey (SWS) using infant and 6-year lung function, and allergic sensitization at 1, 3, and 6 years, comparing these with TCRS phenotypes. METHODS: Complete 6-year follow-up data were available for 926 children, selected from 1,973 infants born to 12,579 women characterized pre-conception. Ninety-five children had V'maxFRC and FEV0.4 measured age 5-14 weeks using rapid compression/raised volume techniques. At 6 years we performed spirometry (n = 791), fractional exhaled nitric oxide (FeNO, n = 589) and methacholine challenge (n = 234). Skin prick testing was performed at 12m, 3 and 6 years (n = 1,494, 1,255, 699, respectively). Using wheeze status questionnaire data at 6m, 12m, 2, 3 and 6 years we classified children into TCRS (never, transient early, persistent, late-onset) and ALSPAC based groups (never, early, transient, intermediate-onset, late-onset, persistent). RESULTS: Amongst ALSPAC groups, persistent and late-onset wheeze were associated with atopy at 3 and 6 years, whilst intermediate-onset wheeze showed earlier atopic association at 1 year; all three were associated with FeNO at 6 years. Persistent wheezers had lower infant (V'maxFRC P < 0.05) and 6-year lung function (FEV1, FEV1/FVC, and FEF(25-75), P < 0.05), whilst late and intermediate-onset wheezers showed no lung function deficits. Transient wheezers were non-atopic but showed persistent lung function deficits (V'maxFRC in infancy, FEV1 and FEF(25-75) at 6 years, all P < 0.05). Those who wheezed only in the first year (early phenotype) showed no lung function deficits. No associations were seen with 6 years bronchial hyper-responsiveness or infancy FEV0.4. CONCLUSION: SWS cohort data validates the statistically derived ALSPAC six-class model. In particular, lung function and atopy successfully differentiate persistent, late-onset and intermediate-onset wheeze, whilst the Tucson "transient early" wheeze phenotype can be sub-classified into groups that reflect early lung function. Since the 4-class model fails to adequately differentiate phenotypes based on lung function and atopy, we propose that strong consideration be given to using the 6-class paradigm for longitudinal outcome work in wheezing with onset in early life