European and United Kingdom COVID-19 pandemic experience: The same but different.

The global healthcare landscape has changed dramatically and rapidly in 2020. This has had an impact upon paediatricians and in particular respiratory paediatricians. The effects in Europe, with its mature healthcare system, have been far faster and greater than most authorities anticipated. Within six weeks of COVID-19 being declared a public health emergency by the World Health Organisation [WHO] in China, Europe had become the new epicentre of disease. A pandemic was finally declared by the WHO on March 11th 2020. Continued international travel combined with the slow response of some political leaders and a variable focus on economic rather than health consequences resulted in varying containment strategies in response to the threat of the initial wave of the pandemic. It is likely that this variation has contributed to widely differing outcomes across Europe. Common to all countries was the stark lack of preparations and initial poor co-ordination of responses between levels of government to this unforeseen but not unheralded global health crisis. In this article we highlight the impact of the first wave of the COVID-19 pandemic in Italy, Austria, Germany, and the United Kingdom.

Factors affecting the growth of infants diagnosed with cystic fibrosis by newborn screening.

BACKGROUND: Newborn screening (NBS) for cystic fibrosis (CF) improves nutritional outcomes. Despite early dietetic intervention some children fail to grow optimally. We report growth from birth to 2 years in a cohort of children diagnosed with CF by NBS and identify the variables that influence future growth. METHODS: One hundred forty-four children were diagnosed with CF by the West Midlands Regional NBS laboratory between November 2007 and October 2014. All anthropometric measurements and microbiology results from the first 2 years were collated as was demographic and CF screening data. Classification modelling was used to identify the key variables in determining future growth. RESULTS: Complete data were available on 129 children. 113 (88%) were pancreatic insufficient (PI) and 16 (12%) pancreatic sufficient (PS). Mean birth weight (z score) was 3.17 kg (- 0.32). There was no significant difference in birth weight (z score) between PI and PS babies: 3.15 kg (- 0.36) vs 3.28 kg (- 0.05); p = 0.33. By the first clinic visit the difference was significant: 3.42 kg (- 1.39) vs 4.60 kg (- 0.48); p < 0.0001. Weight and height remained lower in PI infants in the first year of life. In the first 2 years of life, 18 (14%) infants failed to regain their birth weight z score. The median time to achieve a weight z score of - 2, - 1 and 0 was 18, 33 and 65 weeks respectively. The median times to reach the same z scores for height were 30, 51 and 90 weeks. Birth weight z score, change in weight z score from birth to first clinic, faecal elastase, isolation of Pseudomonas aeruginosa, isolation of Staphylococcus aureus and sweat chloride were the variables identified by the classification models to predict weight and height in the first and second year of life. CONCLUSIONS: Babies with CF have a lower birth weight than the healthy population. For those diagnosed with CF by NBS, the weight difference between PI and PS babies was not significantly different at birth but became so by the first clinic visit. The presence of certain factors, most already identifiable at the first clinic visit can be used to identify infant at increased risk of poor growth.

Parent misperception of control in childhood/adolescent asthma: the Room to Breathe survey.

The aim of our study was to determine how often asthma control is achieved in children and adolescents, and how asthma affects parents' and children's daily lives. Interviews, including the childhood asthma control test (C-ACT), were conducted with 1,284 parents of asthmatic children (aged 4-15 yrs), as well as with the children themselves (aged 8-15 yrs; n=943), in Canada, Greece, Hungary, the Netherlands, South Africa and the UK. Parents reported mild asthma attacks at least weekly in 11% of children, and serious attacks (requiring oral corticosteroids or hospitalisation) at least annually in 35%. Although 73% of parents described their child's asthma as mild or intermittent, 40% of children/adolescents had C-ACT scores ≤ 19, indicating inadequate control, and only 14.7% achieved complete Global Initiative for Asthma (GINA)-defined control and just 9.2% achieved Scottish Intercollegiate Guidelines Network (SIGN)/British Thoracic Society (BTS)-defined control. Guideline-defined asthma control was significantly less common than well-controlled asthma using the C-ACT (p<0.001). Asthma restricted the child's activities in 39% of families and caused lifestyle changes in 70%. Complete asthma control is uncommon in children worldwide. Guideline-defined control measures appear to be more stringent than those defined by C-ACT or families. Overall, parents underestimate their child's asthma severity and overestimate asthma control. This is a major potential barrier to successful asthma treatment in children.

The use of inhaled corticosteroids in the wheezy under 5-year-old child.

Inhaled corticosteroids are established as the most effective long-term anti-inflammatory therapy for asthma. National and international treatment guidelines recommend the use of these agents for long-term asthma control in children. In children <5 years, there are significant difficulties in diagnosing asthma. There are multiple non-asthma causes of wheeze, and there remains a lack of consensus in the description of wheezing phenotypes in this group of children. There is also a relative paucity of data concerning the short- and long-term effectiveness and side-effects in the under-fives: treatment recommendations have drawn heavily from experience of asthma treatment in school-age children and remains controversial. This article discusses the important recent advances in the evidence-base and current expert opinions which are helping to delineate improved outcomes for young children with wheeze.

Childhood evaluation of salmeterol tolerance--a double-blind randomized controlled trial.

Long acting beta(2)-agonists (LABA) are widely used in children with asthma. Data from adults suggest that there is tachyphylaxis particularly to the bronchoprotective effects of LABA. There are no data in children. To determine whether LABA are subject to tachyphylaxis in school-aged children. Children were eligible for participation if they remained symptomatic on 400 microg of beclometasone dipropionate equivalent/day. Participants undertook a 4-wk run in period with open-label fluticasone 100 microg BD via Diskus. Children were then randomized to receive fluticasone 100 microg BD or salmeterol/fluticasone 50/100 microg BD via Diskus in a double-blind manner. Children underwent spirometry, cold air challenge and salbutamol reversibility testing at baseline, 4 and 8 wk. 37/42 children completed the study. There were significant improvements in basal FEV1 (% predicted) in the salmeterol/fluticasone group (n = 21) (+6.4% (95% CI: 2.4-10.5) p = 0.0033) but not in the fluticasone group (n = 16) [+1.2 (95% CI: -3.4 to 5.8) p = 0.5900]. There was a non-significant reduction in fall in FEV1 provoked by cold air in both groups. There was a significant lessening in the acute salbutamol response after 8 wk in the salmeterol/fluticasone group [-11.4% (95% CI: -17.6 to -5.2) p = 0.0010] but not in the fluticasone group [-1.6% (95% CI: -9.8 to 6.6) p = 0.6827]. Salmeterol/fluticasone therapy significantly improves basal FEV(1) in asthmatic children however, there is negligible additional bronchoprotection by week 4 of treatment and there is significant attenuation of salbutamol responsiveness when compared with fluticasone alone. Some of this reduction in salbutamol response may relate to the concurrent improvements in baseline lung function.

Epigenetic control of fetal gene expression.

Each differentiated cell type has its own epigenetic signature, which reflects its genotype, developmental history, and environmental influences, and is ultimately reflected in the phenotype of the cell and organism. Some cells undergo major epigenetic 'reprogramming' during fetal development. The proper, or improper, handling of these highly sensitive periods may have significant short-term and long-term effects on the newborn and his/her progeny. This review highlights the impact of environmental and nutritional factors on the epigenome and the potential effect of epigenetic dysregulation on maternal and fetal pregnancy outcomes, as well as possible long-term implications.

Regional variation of airway hyperresponsiveness in children with asthma.

Families with asthmatic children were recruited to take part in a multi-centre collaborative study into the genetics of asthma. Detailed phenotypic information was collected on all family members including: lung function, anthropomorphic measurements, response to methacholine challenge, skin prick testing, serum IgE measurements and a detailed nurse-administered questionnaire. Families were eligible for entry into the study if they had two children with a doctor-diagnosis of asthma. Bennett/Twin nebulisers were supplied to each centre from a single source and these were calibrated to determine gravimetric nebuliser output prior to use. Asthmatic probands from each centre had similar degrees of asthma severity and atopy. There was no significant difference in the sex ratios or ages of the probands or numbers of parents with a history of smoking in the families recruited at each centre. However, there was a significant difference in the number of children with airway hyperresponsiveness, with 90% of the North Staffordshire group but only 60% of the Sheffield group having a PC20 of <8 mg/ml for methacholine. This difference highlights the difficulty of using families from different centres in genetic and epidemiological studies.

Vascular access in cystic fibrosis--does size matter?

UNLABELLED: Vascular access is an important part of patient management in cystic fibrosis. In most instances, vascular access is straightforward. However, a single bad experience with venepuncture has a lasting impact. Clinical experience suggested that for some individuals a smaller, shorter intravenous catheter (Leaderflex 22G, 0.7 mm 8.0 cm, Vygon) might be a suitable alternative to standard vascular access via a standard long-line (2 Fr or 3 Fr Nutriline, Vygon). METHODS: Between September 2002 and May 2004 we offered a free, fully informed choice between a standard 30 cm long line or a shorter (8 cm) Leaderflex line and audited this change in practice. RESULTS: A total of 56 lines were inserted over the study period. Data were available for 54 of these (22 Leaderflex and 32 standard long lines). Mean and median line survival was omparable. Leaderflex lines survived for a mean of 12.2 days and median of 14 days. Standard long lines survived for a mean of 12.6 days and median of 14 days. DISCUSSION: Leaderflex lines offer a well-tolerated alternative to standard long lines for the administration of a 14-day course of intravenous antibiotics. Their reduced size and cost offer advantages to patients and doctors.

Oxalate (Rumex venosus) poisoning in cattle.

Fifteen range cows died of oxalate poisoning caused by ingestion of Rumex venosus. Ecchymotic and petechial hemorrhages were prominent on the abdominal serosal surfaces. Approximately 2 L of thin, yellowish fluid was in the abdominal cavity, and mesenteric lymph nodes were enlarged and edematous. Other findings included catarrhal abomasitis; enteritis; pale, edematous kidneys; congested lungs; fatty infiltration of the liver; and nephrosis. In the kidneys, birefringent crystals resembling oxalate crystals were demonstrable only when frozen sections were examined.

Carry on doctor.

We report the case of a 13-year-old girl with tuberculosis who developed persistent symptomatic thrombocytopenia whilst being treated with rifampicin and isoniazid. There was widespread agreement that rifampicin was the likely cause of the thrombocytopenia. After discussion with the family we elected to continue treatment as we believed that the potential benefits of continuing treatment outweighed the risks of thrombocytopenia. Despite continued treatment the platelet count returned to normal after a few weeks. We found that thrombocytopaenia may be transient even when therapy is continued and would recommend a watchful waiting strategy to others faced with a similar clinical dilemma.

Asthma severity and atopy: how clear is the relationship?

BACKGROUND: The relationship between asthma severity and atopy is complex. Many studies have failed to show significant relationships between clinical severity or lung function and markers of atopic sensitisation. AIM: To determine whether increasing asthma severity is related to atopic sensitisation in a population of children with asthma. METHODS: A total of 400 children (7-18 years) with asthma were recruited as part of a multicentre study of the genetics of asthma. Detailed phenotypic data were collected on all participants. Associations between measures of asthma severity and atopic sensitisation were sought using multilevel models allowing variation at the individual and family level. RESULTS: Children recruited to the study had a range of asthma severities, with just over a third having mild persistent asthma. The logarithm of total serum IgE was associated with increased asthma severity score, decreased FEV1, increased airways obstruction, risk of hospital admission, and inhaled steroid use. Increasing skin prick test reactivity to a panel of seven aeroallergens was associated with increased risk of hospital admission, use of an inhaled steroid, and airways obstruction. The results remained highly significant after corrections for age, gender, and birth order. CONCLUSIONS: In children with asthma, increasing atopy is associated with increasing asthma severity. However, the relationships between asthma severity and skin prick tests, and asthma severity and total serum IgE values, appear subtly different.

Maternal glutathione S-transferase GSTP1 genotype is a specific predictor of phenotype in children with asthma.

Maternal factors are known to influence the heritability and expression of asthma and atopy. We report the association of maternal, paternal and proband GSTP1 genotype with lung function in 145 Caucasian children with asthma. GSTP1 Val105/Val105 and Ala114/Val114 genotypes in the child were associated with non-significant increases in lung function (forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and the FEV1/FVC ratio). Paternal genotype had no influence on lung function in the child. In contrast, maternal GSTP1 Val105/Val105 genotype was significantly associated with offspring lung function and was strongly predictive of FEV1/FVC (Val105/Val105 105.2%, Ile105/Val105 and Ile105/Ile105 97.9% p=0.006) and maternal GSTP1 Ala114/Val114 genotype was associated with significantly higher FEV1 (Ala114/Val114 109.0%, Ala114/Ala114 99.0% p=0.008), and FEV1/FVC ratios (Ala114/Val114 104.1%, Ala114/Ala114 98.2% p=0.04). The associations between maternal GSTP1 Val105/Val105 genotype and FEV1/FVC and maternal GSTP1 Ala114/Val114 genotype and FEV1 remained significant (p=0.003 and p=0.007) after correction for child and maternal atopic status, passive smoke exposure, smoking during pregnancy, individual and paternal GSTP1 genotype and was independent of transmission to the child. These data support the hypothesis that maternal GSTP1 genotype can act as a specific risk factor which has ex utero consequences for children with asthma. As a child's genotype is not independent of maternal genotype, effects seen in candidate gene studies may be due at least in part to this phenomenon.

Effects of glutathione S-transferase M1, T1 and P1 on lung function in asthmatic families.

RATIONALE: Previous data have suggested that glutathione-S-transferase (GST) genotypes are important in determining the rate of lung function growth in childhood. This effect was most marked in Caucasian children with asthma. OBJECTIVES: We investigated the association of lung function with GSTM1, GSTP1 and GSTT1 genotypes in Caucasian families with asthma. METHODS: Four hundred and eighteen children and 316 parents from 224 Caucasian families were recruited via a child with asthma, the proband. Associations between lung function and GST genotype were determined using multilevel models. RESULTS: There were no observed associations between lung function and GST genotype in parents. However, in the children, the GSTP1 val(105)/val(105) and GSTM1 null genotypes were associated with significantly higher forced expiratory volume in 1 s (FEV(1)) and FVC values as percentage of predicted. This effect was not statistically significant in the probands but was marked in their siblings in whom GSTP1 val(105)/val(105) was associated with 9.4% higher FEV(1) and 10.7% higher FVC (P=0.005 and 0.001, respectively). The GSTM1 null genotype was associated with a 6.7% higher FEV(1) and 4.1% higher FVC (P=0.003 and 0.063, respectively). These effects remained significant after correcting for the confounders of individual atopic status, tobacco smoke exposure and familial aggregation of lung function values. CONCLUSIONS: GSTM1 and GSTP1 genotypes are important determinants of lung function in childhood. The smaller differences seen in probands are predicted by a simple model in which more rapid decline in lung function is seen in these individuals.

Sildenafil as a treatment for pulmonary hypertension.

Severe, chronic pulmonary hypertension in childhood is uncommon, difficult to treat, and carries a poor prognosis. Sildenafil (Viagra, Pfizer) has been used successfully in adults with pulmonary hypertension as monotherapy or in combination with inhaled prostacyclin. Here we report on its use in three children.

Cardioversion by venepuncture in sustained stable supraventricular tachycardia.

Two cases are described of cardioversion from stable supraventricular tachycardia after venepuncture. In both cases usual vagal manoeuvres at home and in the casualty department were unsuccessful. However, attempts to site intravenous cannulas by the attending medical staff terminated his supraventricular tachycardia. Venepuncture is probably the commonest vagal manoeuvre performed in hospital but has not previously been reported as a method of cardioversion.