Peter J.F.M. Merkus

Recombinant Human Deoxyribonuclease in Infants With Respiratory Syncytial Virus Bronchiolitis

BACKGROUNDnTreatment of hospitalized infants with respiratory syncytial virus (RSV) bronchiolitis is mainly supportive. Bronchodilators and systemic steroids are often used but do not reduce the length of hospital stay. Because hypoxia and airways obstruction develop secondary to viscous mucus in infants with RSV bronchiolitis, and because free DNA is present in RSV mucus, we tested the efficacy of the mucolytic drug recombinant human deoxyribonuclease (rhDNase).nnnMETHODSnIn a multicenter, randomized, double-blind, controlled clinical trial, 225 oxygen-dependent infants admitted to the hospital for RSV bronchiolitis were randomly assigned to receive 2.5 mg bid of nebulized rhDNase or placebo until discharge. The primary end point was length of hospital stay. Secondary end points were duration of supplemental oxygen, improvement in symptom score, and number of intensive care admissions.nnnRESULTSnThere were no significant differences between the groups with regard to the length of hospital stay (p = 0.19) or the duration of supplemental oxygen (p = 0.07). The ratio (rhDNase/placebo) of geometric means of length of stay was 1.12 (95% confidence interval, 0.96 to 1.33); for the duration of supplemental oxygen, the ratio was 1.28 (95% confidence interval, 0.97 to 1.68). There were no significant differences in the rate of improvement of the symptom score or in the number of intensive care admissions.nnnCONCLUSIONSnAdministration of rhDNase did not reduce the length of hospital stay or the duration of supplemental oxygen in oxygen-dependent infants with RSV bronchiolitis.

Bronchodilation in infants with malacia or recurrent wheeze

Background: Controversy remains regarding the effectiveness of bronchodilators in wheezy infants. Aims: To assess the effect of inhaled β2 agonists on lung function in infants with malacia or recurrent wheeze, and to determine whether a negative effect of β2 agonists on forced expiratory flow (V′maxFRC) is more pronounced in infants with airway malacia, compared to infants with wheeze. Methods: We retrospectively analysed lung function data of 27 infants: eight with malacia, 19 with recurrent wheeze. Mean (SD) age was 51 (18) weeks. Mean V′maxFRC (in Z score) was assessed before and after inhalation of β2 agonists. Results: Baseline V′maxFRC was below reference values for both groups. Following inhalation of β2 agonists the mean (95% CI) change in mean V′maxFRC in Z scores was −0.10 (−0.26 to 0.05) and −0.33 (−0.55 to −0.11) for the malacia and wheeze group, respectively. Conclusions: In infants with wheeze, inhaled β2 agonists caused a significant reduction in mean V′maxFRC. Infants with malacia were not more likely to worsen after β2 agonists than were infants with recurrent wheeze.

Prenatal maternal psychological stress and childhood asthma and wheezing: a meta-analysis

The aim of this study was to systematically review and meta-analyse observational studies on prenatal maternal psychological stress and the subsequent development of asthma and wheezing in early childhood. All available published literature from 1960 until November 2013 was systematically searched through electronic databases (PubMed, Embase, PsycInfo and Web of Science). All observational studies assessing associations between any form of prenatal maternal psychological stress and respiratory morbidity in the child were included. Data extraction, quality assessment and meta-analyses were performed. The overall meta-analysis included 10 studies and showed that the prevalence of wheezing, asthma and other respiratory symptoms is higher in children of mothers who were exposed to or experienced some form of psychological stress during pregnancy than in mothers who did not (pooled OR 1.56 (95% CI 1.36–1.80)). Comparable results were observed in subgroup analyses of stress exposure, perceived stress, asthma and wheezing. This study demonstrates that prenatal maternal psychological stress is associated with respiratory morbidity, including asthma and wheezing in the child. Future studies examining the early origins of asthma and wheezing need to account for the impact of prenatal maternal stress. Study showing an association between prenatal psychological stress and subsequent respiratory morbidity in children http://ow.ly/USkLN

Effects of childhood respiratory diseases on the anatomical and functional development of the respiratory system

The anatomical and functional development of the lung appears especially vulnerable to a whole range of insults during gestation and the first few years of life. A significant proportion of adult lung disease originates in utero or early infancy. Most publications on this topic are descriptive retrospective studies. An important limitation of these is that structural changes may precede abnormalities in lung function and development of symptoms. Little is known with certainty with respect to the long-term effects of early insults to the respiratory system. Furthermore, the reversibility of the functional and/or structural defects is hardly ever adequately investigated and it is probably not correct to extrapolate findings from adult studies to paediatric pulmonary diseases. Promoting or facilitating optimal lung growth in fetuses and infants and reducing the incidence of lower respiratory tract infection in infancy may reduce the incidence of adult chronic lung disease in generations to come.

Identification of Pseudomonas aeruginosa and Aspergillus fumigatus mono- and co-cultures based on volatile biomarker combinations

Volatile organic compound (VOC) analysis in exhaled breath is proposed as a non-invasive method to detect respiratory infections in cystic fibrosis patients. Since polymicrobial infections are common, we assessed whether we could distinguish Pseudomonas aeruginosa and Aspergillus fumigatus mono- and co-cultures using the VOC emissions. We took headspace samples of P. aeruginosa, A. fumigatus and co-cultures at 16, 24 and 48u2009h after inoculation, in which VOCs were identified by thermal desorption combined with gas chromatography - mass spectrometry. Using multivariate analysis by Partial Least Squares Discriminant Analysis we found distinct VOC biomarker combinations for mono- and co-cultures at each sampling time point, showing that there is an interaction between the two pathogens, with P. aeruginosa dominating the co-culture at 48u2009h. Furthermore, time-independent VOC biomarker combinations were also obtained to predict correct identification of P. aeruginosa and A. fumigatus in mono-culture and in co-culture. This study shows that the VOC combinations in P. aeruginosa and A. fumigatus co-microbial environment are different from those released by these pathogens in mono-culture. Using advanced data analysis techniques such as PLS-DA, time-independent pathogen specific biomarker combinations can be generated that may help to detect mixed respiratory infections in exhaled breath of cystic fibrosis patients.

ERS statement on the multidisciplinary respiratory management of ataxia telangiectasia

Ataxia telangiectasia (A-T) is a rare, progressive, multisystem disease that has a large number of complex and diverse manifestations which vary with age. Patients with A-T die prematurely with the leading causes of death being respiratory diseases and cancer. Respiratory manifestations include immune dysfunction leading to recurrent upper and lower respiratory infections; aspiration resulting from dysfunctional swallowing due to neurodegenerative deficits; inefficient cough; and interstitial lung disease/pulmonary fibrosis. Malnutrition is a significant comorbidity. The increased radiosensitivity and increased risk of cancer should be borne in mind when requesting radiological investigations. Aggressive proactive monitoring and treatment of these various aspects of lung disease under multidisciplinary expertise in the experience of national multidisciplinary clinics internationally forms the basis of this statement on the management of lung disease in A-T. Neurological management is outwith the scope of this document. Complex respiratory manifestations in ataxia telangiectasia require regular, proactive multidisciplinary management http://ow.ly/Solqe

Real-time monitoring of hydrogen cyanide (HCN) and ammonia (NH3) emitted by Pseudomonas aeruginosa

We present the real-time monitoring of hydrogen cyanide (HCN) production from Pseudomonas aeruginosa (P. aeruginosa) strains in vitro, using laser-based photoacoustic spectroscopy. Simultaneously, the production of ammonia (NH3) was measured, and the influence of different factors (e.g. the medium, temperature and antibiotics treatment) was assessed. Both reference strains and clinical isolates of patients with CF were studied, and compared to other pathogens commonly present in lungs/airways of CF patients. Hydrogen cyanide production starts to rise as soon as P. aeruginosa bacteria reach the stationary phase ((9.0-9.5) × 10(9) colony forming units, CFUs), up to concentrations of 14.5 microliters per hour (µlu2009h(-1)). Different strains of P. aeruginosa produced HCN to varying degrees, and addition of tobramycin strongly reduced HCN production within 2u2009h from application. Burkholderia cepacia also produced HCN (up to 0.35µlu2009h(-1) in 9.0u2009 × u200910(9)u2009CFU) while other pathogens (Aspergillus fumigatus, Stenotrophomonas maltophilia, Mycobacterium abscessus) did not produce detectable levels. Our study reveals for the first time a broad overview of the dynamics of the HCN production in vitro.

Hydrogen cyanide emission in the lung by Staphylococcus aureus

Early detection of Pseudomonas aeruginosa in cystic fibrosis (CF) patients is crucial, since eradication in a later stage is extremely difficult [1]. Until now, it has been assumed that hydrogen cyanide (HCN) can be considered as a specific biomarker for P. aeruginosa in exhaled breath [2–5]. Only Burkholderia cepacia is also known to produce HCN in vitro [6, 7], but HCN is not a biomarker for B. cepacia complex infection in vivo [8]. To our knowledge, actual proof that HCN is not produced by other pathogens is lacking. Investigations into the emission of HCN by Staphylococcus aureus, a predominant CF pathogen throughout childhood, have been very limited. In a single report, five strains have been shown to produce low values in vitro [9], and in vivo studies have not been reported. Hydrogen cyanide is produced by S. aureus in vitro and in vivo and is not an exclusive biomarker for P. aeruginosa http://ow.ly/4nsh7y

Using Web-Based Questionnaires and Obstetric Records to Assess General Health Characteristics Among Pregnant Women: A Validation Study

Background Self-reported medical history information is included in many studies. However, data on the validity of Web-based questionnaires assessing medical history are scarce. If proven to be valid, Web-based questionnaires may provide researchers with an efficient means to collect data on this parameter in large populations. Objective The aim of this study was to assess the validity of a Web-based questionnaire on chronic medical conditions, allergies, and blood pressure readings against obstetric records and data from general practitioners. Methods Self-reported questionnaire data were compared with obstetric records for 519 pregnant women participating in the Dutch PRegnancy and Infant DEvelopment (PRIDE) Study from July 2011 through November 2012. These women completed Web-based questionnaires around their first prenatal care visit and in gestational weeks 17 and 34. We calculated kappa statistics (κ) and the observed proportions of positive and negative agreement between the baseline questionnaire and obstetric records for chronic conditions and allergies. In case of inconsistencies between these 2 data sources, medical records from the woman’s general practitioner were consulted as the reference standard. For systolic and diastolic blood pressure, intraclass correlation coefficients (ICCs) were calculated for multiple data points. Results Agreement between the baseline questionnaire and the obstetric record was substantial (κ=.61) for any chronic condition and moderate for any allergy (κ=.51). For specific conditions, we found high observed proportions of negative agreement (range 0.88-1.00) and on average moderate observed proportions of positive agreement with a wide range (range 0.19-0.90). Using the reference standard, the sensitivity of the Web-based questionnaire for chronic conditions and allergies was comparable to or even better than the sensitivity of the obstetric records, in particular for migraine (0.90 vs 0.40, P=.02), asthma (0.86 vs 0.61, P=.04), inhalation allergies (0.92 vs 0.74, P=.003), hay fever (0.90 vs 0.64, P=.001), and allergies to animals (0.89 vs 0.53, P=.01). However, some overreporting of allergies was observed in the questionnaire and for some nonsomatic conditions sensitivity of both measurement instruments was low. The ICCs for blood pressure readings ranged between 0.72 and 0.92 with very small mean differences between the 2 methods of data collection. Conclusions Web-based questionnaires can be used to validly collect data on many chronic disorders, allergies, and blood pressure readings among pregnant women.

Respiratory disease and respiratory physiology: Putting lung function into perspective: Paediatric asthma

Dealing with paediatric asthma in daily practice, we are mostly interested in the airway function: the hallmark of asthma is the variability of airway patency. Various pulmonary function tests (PFT) can be used to quantify airway caliber in asthmatic children. The choice of the test is based on the developmental age of the child, knowledge of the diagnosis/underlying pathophysiology, clinical questions and reasoning, and treatment. PFT is performed to monitor the severity of asthma and the response to therapy, but can also be used as a diagnostic tool, and to study growth and development of the lungs and airways. This review aims to provide clinicians an overview of the differences in assessing PFT in infants and preschool children compared with older cooperative children, which tests are feasible in infants and young children, the limitations of and usefulness of these tests, and of their interpretation in these age groups.