Dorottya Czövek

Effects of respiratory mechanics on the capnogram phases: importance of dynamic compliance of the respiratory system.

IntroductionThe slope of phase III of the capnogram (SIII) relates to progressive emptying of the alveoli, a ventilation/perfusion mismatch, and ventilation inhomogeneity. SIII depends not only on the airway geometry, but also on the dynamic respiratory compliance (Crs); this latter effect has not been evaluated. Accordingly, we established the value of SIII for monitoring airway resistance during mechanical ventilation.MethodsSidestream capnography was performed during mechanical ventilation in patients undergoing elective cardiac surgery (n = 144). The airway resistance (Raw), total respiratory resistance and Crs displayed by the ventilator, the partial pressure of arterial oxygen (PaO2) and SIII were measured in time domain (ST-III) and in a smaller cohort (n = 68) by volumetry (SV-III) with and without normalization to the average CO2 phase III concentration. Measurements were performed at positive end-expiratory pressure (PEEP) levels of 3, 6 and 9 cmH2O in patients with healthy lungs (Group HL), and in patients with respiratory symptoms involving low (Group LC), medium (Group MC) or high Crs (Group HC).ResultsST-III and SV-III exhibited similar PEEP dependencies and distribution between the protocol groups formed on the basis of Crs. A wide interindividual scatter was observed in the overall Raw-ST-III relationship, which was primarily affected by Crs. Decreases in Raw with increasing PEEP were reflected in sharp falls in SIII in Group HC, and in moderate decreases in SIII in Group MC, whereas ST-III was insensitive to changes in airway caliber in Groups LC and HL.ConclusionsSIII assessed in the time domain and by volumetry provide meaningful information about alterations in airway caliber, but only within an individual patient. Although ST-III may be of value for bedside monitoring of the airway properties, its sensitivity depends on Crs. Thus, assessment of the capnogram shape should always be coupled with Crs when the airway resistance or oxygenation are evaluated.

Lung function and exhaled nitric oxide in healthy unsedated African infants

Population‐appropriate lung function reference data are essential to accurately identify respiratory disease and measure response to interventions. There are currently no reference data in African infants. The aim was to describe normal lung function in healthy African infants.

Respiratory impedance in healthy unsedated South African infants: Effects of maternal smoking

Non‐invasive techniques for measuring lung mechanics in infants are needed for a better understanding of lung growth and function, and to study the effects of prenatal factors on subsequent lung growth in healthy infants. The forced oscillation technique requires minimal cooperation from the individual but has rarely been used in infants. The study aims to assess the use of the forced oscillation technique to measure the influence of antenatal exposures on respiratory mechanics in unsedated infants enrolled in a birth cohort study in Cape Town, South Africa.

Assessment of respiratory mechanics with forced oscillations in healthy newborns

Lung function data in healthy newborn infants are scarce largely due to lack of suitable techniques, although data for developmental and prenatal exposure studies are much needed. We have modified the forced oscillation technique (FOT) for the measurement of respiratory mechanical impedance (Zrs) in unsedated sleeping infants in the first 3 days of life.

Tidal changes in respiratory resistance are sensitive indicators of airway obstruction in children

Rationale Individual assessment of airway obstruction in preschool-age children requires sensitive and specific lung function methods with low demand of cooperation. Although the forced oscillation technique (FOT) is feasible in young children, conventional measurements of respiratory impedance (Zrs) have limited diagnostic power in individuals. Objective To find descriptors of within-breath Zrs that are sensitive indicators of airway obstruction during tidal breathing in children. Methods Zrs was measured with (i) a standard multifrequency FOT (4–26 Hz) to assess the mean values of resistance and reactance for whole breaths and (ii) a 10 Hz signal to track the within-breath changes. Various Zrs measures obtained in healthy children (n=75) and those with acute wheeze (n=31) were investigated with receiver operator characteristic (ROC) analysis. The cut-off values obtained for airway obstruction were then tested in children with recurrent wheeze (n=20) before and after administration of salbutamol. Results The largest area under the ROC curve (0.95) was observed for the tidal changes of resistance between the zero-flow values (ΔR). The ΔR cut-off value of 1.42 hPa s/L detected airway obstruction with sensitivity of 92% and specificity of 89% in children with acute wheeze and distinguished children with recurrent wheeze (16/20 above the cut-off value) from healthy children (22/23 below the cut-off value). Furthermore, ΔR significantly decreased after salbutamol in wheezy children but remained unchanged in healthy children. Conclusions New lung function measure ΔR is able to detect airway obstruction with high sensitivity and specificity and is suitable for use in lung function testing in young children.

Respiratory consequences of red sludge dust inhalation in rats

The environmental disaster following flooding by red sludge in the Ajka region in Hungary poses a serious public health threat with particular concern regarding the potentially adverse respiratory effects of the inhalation of red sludge dust (RSD). The respiratory consequences of the inhalation of RSD obtained from field samples were investigated in rats. Rats were either exposed to RSD at a high concentration (2 weeks, 8h/day), or kept in room air. After the exposures, the airway resistance (R(aw)) and the respiratory tissues mechanics were measured under baseline condition, and following methacholine (MCh) challenges with the aim of establishing airway hyper-responsiveness (AH). Histopathology was performed to assess lung morphologic alterations. The physical properties and the chemical composition of the RSD were also characterized. The size distribution, chemical composition and topology of the RSD particles applied in our experiments were similar to those observed at the site of the disaster. The inhalation of RSD did not alter the basal respiratory mechanics, whereas it led to greater MCh-induced responses in R(aw), demonstrating the progression of mild AH. Histopathological investigations revealed fine, granular particles in the alveolar macrophages, as evidence that RSD had reached the lower respiratory tract and induced mild inflammation around the alveoli and the pulmonary vasculature. The mild respiratory symptoms that developed following short-term exposure of healthy individuals to high concentrations of airborne RSD do not appear to pose a greater respiratory hazard than the inhalation of urban dust at a comparable concentration.

Determinants of early-life lung function in African infants.

Background Low lung function in early life is associated with later respiratory illness. There is limited data on lung function in African infants despite a high prevalence of respiratory disease. Aim To assess the determinants of early lung function in African infants. Method Infants enrolled in a South African birth cohort, the Drakenstein child health study, had lung function measured at 6–10 weeks of age. Measurements, made with the infant breathing via a facemask during natural sleep, included tidal breathing, sulfur hexafluoride multiple breath washout and the forced oscillation technique. Information on antenatal and early postnatal exposures was collected using questionnaires and urine cotinine. Household benzene exposure was measured antenatally. Results Successful tests were obtained in 645/675 (95%) infants, median (IQR) age of 51 (46–58) days. Infant size, age and male gender were associated with larger tidal volume. Infants whose mothers smoked had lower tidal volumes (−1.6 mL (95% CI −3.0 to −0.1), p=0.04) and higher lung clearance index (0.1 turnovers (95% CI 0.01 to 0.3), p=0.03) compared with infants unexposed to tobacco smoke. Infants exposed to alcohol in utero or household benzene had lower time to peak tidal expiratory flow over total expiratory time ratios, 10% (95% CI −15.4% to −3.7%), p=0.002) and 3.0% (95% CI −5.2% to −0.7%, p=0.01) lower respectively compared with unexposed infants. HIV-exposed infants had higher tidal volumes (1.7 mL (95% CI 0.06 to 3.3) p=0.04) compared with infants whose mothers were HIV negative. Conclusion We identified several factors including infant size, sex, maternal smoking, maternal alcohol, maternal HIV and household benzene associated with altered early lung function, many of which are factors amenable to public health interventions. Long-term study of lung function and respiratory disease in these children is a priority to develop strategies to strengthen child health.

Spirometry and forced oscillations in the detection of airway hyperreactivity in asthmatic children

Provocation tests are routinely used to detect airway hyperreactivity (AH) in the diagnosis of asthma. We compared the sensitivities of the forced oscillation technique (FOT) and spirometry in the detection of AH in asthmatic children.

Loss of ATM in Airway Epithelial Cells Is Associated with Susceptibility to Oxidative Stress

Ataxia-telangiectasia (A-T) is characterized by chromosomal instability, immunodeficiency, cancer susceptibility, neurodegeneration, and pulmonary disease (1). One of the cardinal features of A-T is recurrent sinopulmonary infection, which is associated with the development of bronchiectasis and interstitial lung disease (2). Respiratory disease causes significant morbidity and mortality in patients with A-T, being responsible for up to 40% of deaths (3). Respiratory infections with Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa, and Haemophilus influenzae have been reported (4). A recent report showed that S. pneumoniae caused DNA damage and apoptosis in lung cells by secretion of H2O2, an agent known to cause oxidative stress (5). In this context, there is accumulating evidence that oxidative stress is associated with A-T disease, including increased sensitivity to oxidative damage, elevated levels of reactive oxygen species in A-T cells, protection against damage by antioxidants, and the observation that ataxia-telangiectasia mutated (ATM), the protein defective in A-T, is activated by oxidative stress (6–9). On the basis of these observations, the aim of this pilot study was to determine whether airway epithelial cells from patients with A-T show increased susceptibility to oxidative stress. Some of the results of these studies have been previously reported in the form of an abstract (10).

Defining ‘healthy’ in preschool‐aged children for forced oscillation technique reference equations

Selecting ‘healthy’ preschool‐aged children for reference ranges may not be straightforward. Relaxing inclusion criteria for normative data does not affect spirometry z‐scores. We therefore investigated the effect of similarly relaxing inclusion criteria in preschoolers on reference ranges for respiratory impedance (Zrs) using a modified forced oscillation technique (FOT).