Claudia E. Kuehni

Primary ciliary dyskinesia: a consensus statement on diagnostic and treatment approaches in children.

Primary ciliary dyskinesia (PCD) is associated with abnormal ciliary structure and function, which results in retention of mucus and bacteria in the respiratory tract, leading to chronic oto-sino-pulmonary disease, situs abnormalities and abnormal sperm motility. The diagnosis of PCD requires the presence of the characteristic clinical phenotype and either specific ultrastructural ciliary defects identified by transmission electron microscopy or evidence of abnormal ciliary function. Although the management of children affected with PCD remains uncertain and evidence is limited, it remains important to follow-up these patients with an adequate and shared care system in order to prevent future lung damage. This European Respiratory Society consensus statement on the management of children with PCD formulates recommendations regarding diagnostic and therapeutic approaches in order to permit a more accurate approach in these patients. Large well-designed randomised controlled trials, with clear description of patients, are required in order to improve these recommendations on diagnostic and treatment approaches in this disease.

Are all wheezing disorders in very young (preschool) children increasing in prevalence

BACKGROUND Distinct wheezing disorders co-exist in young (preschool) children, some of which (early transient wheeze and viral wheeze) are thought to be unrelated to atopy. Investigation of changes in prevalence of wheezing disorders in preschool children could provide important clues about underlying mechanisms responsible for increasing prevalence of asthma in schoolchildren. METHODS Repeated population surveys of the prevalence of respiratory symptoms were done by parent-completed postal questionnaires in random samples of 1650 (1990) and 2600 (1998) caucasian children aged 1-5 years living in the county of Leicestershire, UK. FINDINGS The response rates were 86% (1422 of 1650) in 1990 and 84% (2127 of 2522) in 1998. Between 1990 and 1998, there was a significant increase in the prevalance of reported wheeze ever (16% to 29%, p<0.0001), current wheeze (12% to 26%, p<0.0001), diagnosis of asthma (11% to 19%, p<0.0001), treatment for wheeze (15% to 26%, p<0.0001), and admission for wheeze or other chest trouble (6% to 10%, p<0.0001). The increase occurred both in children with viral wheeze (9% to 19%) and in those with the classic asthma pattern of wheezing with multiple triggers (6% to 10%). There was also an increase in transient early wheezers (3% to 5%), persistent wheezers (5% to 13%), and late-onset wheezers (6% to 8%), and in all severity groups. The increase could not be accounted for by putative household risk factors because these declined between the 2 years. INTERPRETATION The fact that all preschool wheezing disorders increased (including viral wheeze) makes it probable that factors unrelated to atopy are implicated in the changing epidemiology of wheeze in childhood.

Does Pet Ownership in Infancy Lead to Asthma or Allergy at School Age? Pooled Analysis of Individual Participant Data from 11 European Birth Cohorts

Objective To examine the associations between pet keeping in early childhood and asthma and allergies in children aged 6–10 years. Design Pooled analysis of individual participant data of 11 prospective European birth cohorts that recruited a total of over 22,000 children in the 1990s. Exposure definition Ownership of only cats, dogs, birds, rodents, or cats/dogs combined during the first 2 years of life. Outcome definition Current asthma (primary outcome), allergic asthma, allergic rhinitis and allergic sensitization during 6–10 years of age. Data synthesis Three-step approach: (i) Common definition of outcome and exposure variables across cohorts; (ii) calculation of adjusted effect estimates for each cohort; (iii) pooling of effect estimates by using random effects meta-analysis models. Results We found no association between furry and feathered pet keeping early in life and asthma in school age. For example, the odds ratio for asthma comparing cat ownership with “no pets” (10 studies, 11489 participants) was 1.00 (95% confidence interval 0.78 to 1.28) (I2 = 9%; p = 0.36). The odds ratio for asthma comparing dog ownership with “no pets” (9 studies, 11433 participants) was 0.77 (0.58 to 1.03) (I2 = 0%, p = 0.89). Owning both cat(s) and dog(s) compared to “no pets” resulted in an odds ratio of 1.04 (0.59 to 1.84) (I2 = 33%, p = 0.18). Similarly, for allergic asthma and for allergic rhinitis we did not find associations regarding any type of pet ownership early in life. However, we found some evidence for an association between ownership of furry pets during the first 2 years of life and reduced likelihood of becoming sensitized to aero-allergens. Conclusions Pet ownership in early life did not appear to either increase or reduce the risk of asthma or allergic rhinitis symptoms in children aged 6–10. Advice from health care practitioners to avoid or to specifically acquire pets for primary prevention of asthma or allergic rhinitis in children should not be given.

Distinguishing phenotypes of childhood wheeze and cough using latent class analysis

Airway disease in childhood comprises a heterogeneous group of disorders. Attempts to distinguish different phenotypes have generally considered few disease dimensions. The present study examines phenotypes of childhood wheeze and chronic cough, by fitting a statistical model to data representing multiple disease dimensions. From a population-based, longitudinal cohort study of 1,650 preschool children, 319 with parent-reported wheeze or chronic cough were included. Phenotypes were identified by latent class analysis using data on symptoms, skin-prick tests, lung function and airway responsiveness from two preschool surveys. These phenotypes were then compared with respect to outcome at school age. The model distinguished three phenotypes of wheeze and two phenotypes of chronic cough. Subsequent wheeze, chronic cough and inhaler use at school age differed clearly between the five phenotypes. The wheeze phenotypes shared features with previously described entities and partly reconciled discrepancies between existing sets of phenotype labels. This novel, multidimensional approach has the potential to identify clinically relevant phenotypes, not only in paediatric disorders but also in adult obstructive airway diseases, where phenotype definition is an equally important issue.

Factors influencing age at diagnosis of primary ciliary dyskinesia in European children.

Primary ciliary dyskinesia (PCD) is a hereditary disorder of mucociliary clearance causing chronic upper and lower airways disease. We determined the number of patients with diagnosed PCD across Europe, described age at diagnosis and determined risk factors for late diagnosis. Centres treating children with PCD in Europe answered questionnaires and provided anonymous patient lists. In total, 223 centres from 26 countries reported 1,009 patients aged <20 yrs. Reported cases per million children (for 5–14 yr olds) were highest in Cyprus (111), Switzerland (47) and Denmark (46). Overall, 57% were males and 48% had situs inversus. Median age at diagnosis was 5.3 yrs, lower in children with situs inversus (3.5 versus 5.8 yrs; p<0.001) and in children treated in large centres (4.1 versus 4.8 yrs; p = 0.002). Adjusted age at diagnosis was 5.0 yrs in Western Europe, 4.8 yrs in the British Isles, 5.5 yrs in Northern Europe, 6.8 yrs in Eastern Europe and 6.5 yrs in Southern Europe (p<0.001). This strongly correlated with general government expenditures on health (p<0.001). This European survey suggests that PCD in children is under-diagnosed and diagnosed late, particularly in countries with low health expenditures. Prospective studies should assess the impact this delay might have on patient prognosis and on health economic costs across Europe.

Mobile Phone Use and Brain Tumors in Children and Adolescents: A Multicenter Case–Control Study

BACKGROUND It has been hypothesized that children and adolescents might be more vulnerable to possible health effects from mobile phone exposure than adults. We investigated whether mobile phone use is associated with brain tumor risk among children and adolescents. METHODS CEFALO is a multicenter case-control study conducted in Denmark, Sweden, Norway, and Switzerland that includes all children and adolescents aged 7-19 years who were diagnosed with a brain tumor between 2004 and 2008. We conducted interviews, in person, with 352 case patients (participation rate: 83%) and 646 control subjects (participation rate: 71%) and their parents. Control subjects were randomly selected from population registries and matched by age, sex, and geographical region. We asked about mobile phone use and included mobile phone operator records when available. Odds ratios (ORs) for brain tumor risk and 95% confidence intervals (CIs) were calculated using conditional logistic regression models. RESULTS Regular users of mobile phones were not statistically significantly more likely to have been diagnosed with brain tumors compared with nonusers (OR = 1.36; 95% CI = 0.92 to 2.02). Children who started to use mobile phones at least 5 years ago were not at increased risk compared with those who had never regularly used mobile phones (OR = 1.26, 95% CI = 0.70 to 2.28). In a subset of study participants for whom operator recorded data were available, brain tumor risk was related to the time elapsed since the mobile phone subscription was started but not to amount of use. No increased risk of brain tumors was observed for brain areas receiving the highest amount of exposure. CONCLUSION The absence of an exposure-response relationship either in terms of the amount of mobile phone use or by localization of the brain tumor argues against a causal association.

Alveolarization Continues during Childhood and Adolescence: New Evidence from Helium-3 Magnetic Resonance

RATIONALE The current hypothesis that human pulmonary alveolarization is complete by 3 years is contradicted by new evidence of alveolarization throughout adolescence in mammals. OBJECTIVES We reexamined the current hypothesis using helium-3 ((3)He) magnetic resonance (MR) to assess alveolar size noninvasively between 7 and 21 years, during which lung volume nearly quadruples. If new alveolarization does not occur, alveolar size should increase to the same extent. METHODS Lung volumes were measured by spirometry and plethysmography in 109 healthy subjects aged 7-21 years. Using (3)HeMR we determined two independent measures of peripheral airspace dimensions: apparent diffusion coefficient (ADC) of (3)He at FRC (n = 109), and average diffusion distance of helium (X(rms)) by q-space analysis (n = 46). We compared the change in these parameters with lung growth against a model of lung expansion with no new alveolarization. MEASUREMENTS AND MAIN RESULTS ADC increased by 0.19% for every 1% increment in FRC (95% confidence interval [CI], 0.13-0.25), whereas the expected change in the absence of neoalveolarization is 0.41% (95% CI, 0.31-0.52). Similarly, increase of (X(rms)) with FRC was significantly less than the predicted increase in the absence of neoalveolarization. The number of alveoli is estimated to increase 1.94-fold (95% CI, 1.64-2.30) across the age range studied. CONCLUSIONS Our observations are best explained by postulating that the lungs grow partly by neoalveolarization throughout childhood and adolescence. This has important implications: developing lungs have the potential to recover from early life insults and respond to emerging alveolar therapies. Conversely, drugs, diseases, or environmental exposures could adversely affect alveolarization throughout childhood.

Viral etiology of acute respiratory infections with cough in infancy: a community-based birth cohort study

Background: Acute respiratory infections (ARI) are a major cause of morbidity in infancy worldwide, with cough and wheeze being alarming symptoms to parents. We aimed to analyze in detail the viral aetiology of ARI with such symptoms in otherwise healthy infants, including rhinoviruses and recently discovered viruses such as human metapneumovirus (HMPV), coronavirus NL63 and HKU1, and human bocavirus (HBoV). Methods: We prospectively followed 197 unselected infants during their first year of life and assessed clinical symptoms by weekly standardized interviews. At the first ARI with cough or wheeze, we analyzed nasal swabs by sensitive individual real time polymerase chain reaction assays targeting 16 different respiratory viruses. Results: All 112 infants who had an ARI had cough, and 39 (35%) had wheeze. One or more respiratory viruses were found in 88 of 112 (79%) cases. Fifteen (17%) dual and 3 (3%) triple infections were recorded. Rhino- (23% of all viruses) and coronaviruses (18%) were most common, followed by parainfluenza viruses (17%), respiratory syncytial virus (RSV) (16%), HMPV (13%), and HBoV (5%). Together rhinoviruses, coronaviruses, HMPV, and HBoV accounted for 60% (65 of 109) of viruses. Although symptom scores and need for general practitioner (GP) consultations were highest in infants infected with RSV, they were similar in infants infected with other viruses. Viral shedding at 3 weeks occurred in 20% of cases. Conclusions: Rhinoviruses, coronaviruses, HMPV, and HBoV are common pathogens associated with respiratory symptoms in otherwise healthy infants. They should be considered in the differential diagnosis of the aetiology of ARI in this age group.

Air pollution during pregnancy and lung function in newborns: a birth cohort study

Post-natal exposure to air pollution is associated with diminished lung growth during school age. The current authors aimed to determine whether pre-natal exposure to air pollution is associated with lung function changes in the newborn. In a prospective birth cohort of 241 healthy term-born neonates, tidal breathing, lung volume, ventilation inhomogeneity and exhaled nitric oxide (eNO) were measured during unsedated sleep at age 5 weeks. Maternal exposure to particles with a 50% cut-off aerodynamic diameter of 10 μm (PM10), nitrogen dioxide (NO2) and ozone (O3), and distance to major roads were estimated during pregnancy. The association between these exposures and lung function was assessed using linear regression. Minute ventilation was higher in infants with higher pre-natal PM10 exposure (24.9 mL·min−1 per μg·m−3 PM10). The eNO was increased in infants with higher pre-natal NO2 exposure (0.98 ppb per μg·m−3 NO2). Post-natal exposure to air pollution did not modify these findings. No association was found for pre-natal exposure to O3 and lung function parameters. The present results suggest that pre-natal exposure to air pollution might be associated with higher respiratory need and airway inflammation in newborns. Such alterations during early lung development may be important regarding long-term respiratory morbidity.

Age-related differences in perceived asthma control in childhood: guidelines and reality

Current guidelines specify the goals of asthma treatment in children and propose a stepwise approach to achieve them. The authors sought to determine whether these goals were attained in children of different age groups in the community and to assess treatment in those with unsatisfactory asthma control. A cross-sectional postal questionnaire survey was performed in 1998 in all members of the major Swiss parents organisation for childhood asthma. With a response rate of 85%, data from 572 Swiss-German children aged 4–16 yrs with wheeze were analysed. Asthma control was excellent in 18% of the children, satisfactory (only episodic symptoms) in 33%, and unsatisfactory in 49% with disturbed sleep, restricted activities and school absences. When stratified by age, excellent or satisfactory control was attained by 66% of children aged 13–16 yrs, but only by 56%, 44%, and 38% of those aged 10–12, 7–9 and 4–6 yrs, respectively. Although the majority were followed-up by a doctor (95%) and were receiving β2-agonists (82%) and inhaled corticosteroids (68%), intensity and duration of treatment were not sufficiently matched to asthma severity. In virtually all children there was scope to improve medical treatment, preventive measures and knowledge of asthma management, with very few if any children with therapy-resistant asthma. Even in children with poor asthma control, 89% of parents were satisfied with the results of treatment. The goals of asthma treatment were attained in one-half of the children, particularly in younger age groups. Although inhaler use was common, detailed assessment showed evidence for undertreatment, especially in the youngest age group, and insufficient adherence to preventive measures. Parental expectations of asthma control, which were lower than those outlined in guidelines, might be an important but underestimated factor in paediatric asthma management.