Using intra-breath oscillometry in obesity hypoventilation syndrome to detect tidal expiratory flow limitation: a potential marker to optimize CPAP therapy.

BACKGROUND: Continuous positive airway pressure (CPAP) therapy has profound effects in obesity hypoventilation syndrome (OHS). Current therapy initiation focuses on upper airway patency rather than the assessment of altered respiratory mechanics due to increased extrapulmonary mechanical load. METHODS: We aimed to examine the viability of intra-breath oscillometry in optimizing CPAP therapy for OHS. We performed intra-breath oscillometry at 10 Hz in the sitting and supine positions, followed by measurements at increasing CPAP levels (none-5-10-15-20 cmH2O) in awake OHS patients. We plotted intra-breath resistance and reactance (Xrs) values against flow (V') and volume (V) to identify tidal expiratory flow limitation (tEFL). RESULTS: Thirty-five patients (65.7% male) completed the study. We found a characteristic looping of the Xrs vs V' plot in all patients in the supine position revealing tEFL: Xrs fell with decreasing flow at end-expiration. Intra-breath variables representing expiratory decrease of Xrs became more negative in the supine position [end-expiratory Xrs (mean ± SD): -1.9 ± 1.8 cmH2O·s·L- 1 sitting vs. -4.2 ± 2.2 cmH2O·s·L- 1 supine; difference between end-expiratory and end-inspiratory Xrs: -1.3 ± 1.7 cmH2O·s·L- 1 sitting vs. -3.6 ± 2.0 cmH2O·s·L- 1 supine, p < 0.001]. Increasing CPAP altered expiratory Xrs values and loop areas, suggesting diminished tEFL (p < 0.001). 'Optimal CPAP' value (able to cease tEFL) was 14.8 ± 4.1 cmH2O in our cohort, close to the long-term support average of 13.01(± 2.97) cmH2O but not correlated. We found no correlation between forced spirometry values, patient characteristics, apnea-hypopnea index and intra-breath oscillometry variables. CONCLUSIONS: tEFL, worsened by the supine position, can be diminished by stepwise CPAP application in most patients. Intra-breath oscillometry is a viable method to detect tEFL during CPAP initiation in OHS patients and tEFL is a possible target for optimizing therapy in OHS patients.

Respiratory Oscillometry in Newborn Infants: Conventional and Intra-Breath Approaches.

Background: Oscillometry has been employed widely as a non-invasive and standardized measurement of respiratory function in children and adults; however, limited information is available on infants. Aims: To establish the within-session variability of respiratory impedance (Zrs), to characterize the degree and profile of intra-breath changes in Zrs and to assess their impact on conventional oscillometry in newborns. Methods: 109 healthy newborns were enrolled in the study conducted in the first 5 postpartum days during natural sleep. A custom-made wave-tube oscillometry setup was used, with an 8-48 Hz pseudorandom and a 16 Hz sinusoidal signal used for spectral and intra-breath oscillometry, respectively. A resistance-compliance-inertance (R-C-L) model was fitted to average Zrs spectra obtained from successive 30-s recordings. Intra-breath measures, such as resistance (Rrs) and reactance (Xrs) at the end-expiratory, end-inspiratory and maximum-flow points were estimated from three 90-s recordings. All natural and artifact-free breaths were included in the analysis. Results: Within-session changes in the mean R, C and L values, respectively, were large (mean coefficients of variation: 10.3, 20.3, and 26.6%); the fluctuations of the intra-breath measures were of similar degree (20-24%). Intra-breath analysis also revealed large swings in Rrs and Xrs within the breathing cycle: the peak-to-peak changes amounted to 93% (range: 32-218%) and 41% (9-212%), respectively, of the zero-flow Zrs magnitude. Discussion: Intra-breath tracking of Zrs provides new insight into the determinants of the dynamics of respiratory system, and highlights the biasing effects of mechanical non-linearities on the average Zrs data obtained from the conventional spectral oscillometry.

Efficacy of nusinersen in type 1, 2 and 3 spinal muscular atrophy: Real world data from Hungarian patients.

INTRODUCTION: Spinal muscular atrophy (SMA) is an autosomal recessive disorder caused by a homozygous deletion of the survival motor neuron (SMN) 1 gene. Nusinersen is an antisense oligonucleotide enhancing the production of the SMN protein. It has received approval by the European Medicines Agency (EMA) in 2017, based on the clinical trials demonstrating the effectiveness of nusinersen in several types of SMA. In Hungary, the first patient received nusinersen treatment in April 2018. Our aim is to summarize our experience regarding the efficacy, safety and tolerability of nusinersen in our patients. METHODS: Data were collected retrospectively in all types of SMA patients (type 1-3) starting treatment with nusinersen in Hungary between April 2018 and December 2019. Motor functions were evaluated at baseline, at the fourth and all following injections. RESULTS: By 31st December 2019, nusinersen therapy was initiated in 54 patients at either of the two Hungarian treatment centres. Mean age of the patients at the start of the treatment was 6.3 years (±5,4 range 0.4-17.9). 13 patients are type 1 (mean 0.78 ± 0.27, range 0.4-1.5 yrs), 21 patients are type 2 (mean 4.5 ± 3.3, range 1.3-12 yrs), 23 patients are type 3 (mean 10.9 ± 5.2, range 2.9-17.9 yrs). Fourteen patients had severe scoliosis, four of them underwent spine stabilizing surgery. During the study period 340 injections were administered without any new safety concerns emerging. The data of 38 patients, who had completed the first six treatments, were included in the final statistical analysis. Motor function has improved in most of the children. By the 307th day visit, on average, a 14.9 (±5,1) point improvement was measured on the CHOP INTEND scale in type 1 patients (p = 0.016). All patients with type 1 SMA who performed the motor evaluation (7/10) have improved by more than four (7-21) points. Regarding type 2 patients, a 7.2 (range -2- 17) point increase from baseline (p < 0.001) on the Hammersmith Functional Motor Scale Expanded (HFMSE) and 4.3 (range: 2-9) point increase (p = 0.031) on the Revised Upper Limb Module (RULM) were found. The distance of the 6 min walk test also increased by 33.9 m on average (range -16 - 106), in type 3 patients. CONCLUSION: According to our results nusinersen has the same safety and tolerability profile as in the clinical trials. In a heterogenic patient population of SMA type 1 and 2, nusinersen showed similar efficacy as seen in the pivotal studies. A clinically and statistically significant improvement of motor functions was also detectable in type 3 patients with heterogeneous age distribution.

Intra-breath measures of respiratory mechanics in healthy African infants detect risk of respiratory illness in early life.

Lower respiratory tract illness (LRTI) is a leading cause of mortality and morbidity in children. Sensitive and noninvasive infant lung function techniques are needed to measure risk for and impact of LRTI on lung health. The objective of this study was to investigate whether lung function derived from the intra-breath forced oscillation technique (FOT) was able to identify healthy infants at risk of LRTI in the first year of life.Lung function was measured with the novel intra-breath FOT, in 6-week-old infants in a South African birth cohort (Drakenstein Child Health Study). LRTI during the first year was confirmed by study staff. The association between baseline lung function and LRTI was assessed with logistic regression and odds ratios determined using optimal cut-off values.Of the 627 healthy infants with successful lung function testing, 161 (24%) had 238 LRTI episodes subsequently during the first year. Volume dependence of respiratory resistance (ΔR) and reactance (ΔX) was associated with LRTI. The predictive value was stronger if LRTI was recurrent (n=50 (31%): OR 2.5, ΔX), required hospitalisation (n=38 (16%): OR 5.4, ΔR) or was associated with wheeze (n=87 (37%): OR 3.9, ΔX).Intra-breath FOT can identify healthy infants at risk of developing LRTI, wheezing or severe illness in the first year of life.

Defining 'healthy' in preschool-aged children for forced oscillation technique reference equations.

BACKGROUND AND OBJECTIVE: 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). METHODS: The International Study of Asthma and Allergies in Childhood questionnaire classified 585 children into a healthy and five mutually exclusive groups. Zrs was measured between 4 and 26 Hz and resistance (R) and compliance (C) obtained by model fitting. Prediction models were determined using mixed effect models and z-scores compared between healthy children and the five groups. RESULTS: Zrs data were obtained for 494 participants (4.30 ± 0.7 years) on 587 occasions. Comparison of the Zrs z-scores between the healthy children and the health groups found significant differences in children with asthma, current wheeze and respiratory symptoms, but not in children born preterm or with early-life wheeze. Adding these two groups to the healthy dataset had no significant effect on the distribution of z-scores and increased the size of the dataset by 22.3%. CONCLUSION: Our data suggest that preschool-aged children born preterm or with early-life wheeze can be included in FOT reference equations, while those with asthma, current wheeze and respiratory symptoms within 4 weeks of testing should be excluded. This more inclusive approach results in more robust FOT reference ranges.

Airway dynamics in COPD patients by within-breath impedance tracking: effects of continuous positive airway pressure.

Tracking of the within-breath changes of respiratory mechanics using the forced oscillation technique may provide outcomes that characterise the dynamic behaviour of the airways during normal breathing.We measured respiratory resistance (Rrs) and reactance (Xrs) at 8 Hz in 55 chronic obstructive pulmonary disease (COPD) patients and 20 healthy controls, and evaluated Rrs and Xrs as functions of gas flow (V') and volume (V) during normal breathing cycles. In 12 COPD patients, additional measurements were made at continuous positive airway pressure (CPAP) levels of 4, 8, 14 and 20 hPa.The Rrs and Xrsversus V' and V relationships displayed a variety of loop patterns, allowing characterisation of physiological and pathological processes. The main outcomes emerging from the within-breath analysis were the Xrsversus V loop area (AXV) quantifying expiratory flow limitation, and the tidal change in Xrs during inspiration (ΔXI) reflecting alteration in lung inhomogeneity in COPD. With increasing CPAP, AXV and ΔXI approached the normal ranges, although with a large variability between individuals, whereas mean Rrs remained unchanged.Within-breath tracking of Rrs and Xrs allows an improved assessment of expiratory flow limitation and functional inhomogeneity in COPD; thereby it may help identify the physiological phenotypes of COPD and determine the optimal level of respiratory support.

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.

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.

Fluid replacement and respiratory function: comparison of whole blood with colloid and crystalloid: A randomised animal study.

BACKGROUND: Fluid replacement with blood products, colloids and crystalloids is associated with morbidity and mortality. Despite this, the consequences of fluid administration on airway and respiratory tissue properties are not fully understood. OBJECTIVE: Comparison of respiratory effects of fluid replacement with autologous blood (Group B), colloid (HES 6% 130/0.4, Group CO) or crystalloid solution (NaCl 0.9%, Group CR) after haemorrhage with separate assessments of airway resistance and respiratory tissue mechanics. DESIGN: A randomised study. SETTING: An experimental model of surgical haemorrhage and fluid replacement in rats. PARTICIPANTS: Anaesthetised, ventilated rats randomly allocated into three groups (Group B: n = 8, Group CO: n = 8, Group CR: n = 9). INTERVENTION: Animals were bled in six sequential steps, each manoeuvre targeting a loss of 5% of total blood volume. The blood loss was then replaced stepwise in a 1 : 1 ratio with one of the three fluids. MAIN OUTCOME MEASURE: After each step, airway resistance (Raw), tissue damping and elastance (H) were determined by forced oscillations. Oedema indices from lung weights and histology were also measured. RESULTS: Raw (mean ±â€ŠSD) decreased in all groups following blood loss (-20.3 ±â€Š9.5% vs. baseline, P < 0.05), and remained low following blood replacement (-21.7 ±â€Š14.5% vs. baseline, P < 0.05), but was normalised by colloid (5.5 ±â€Š10.7%, NS). Crystalloid administration exhibited an intermediate reversal effect (-8.4 ±â€Š14.7%, NS). Tissue viscoelasticity increased following both blood loss and replacement, with no evidence of a significant difference in H between Groups CO and CR. More severe oedema was observed in Groups CR and CO than in Group B (P < 0.05), with no difference between the colloid and crystalloid solutions. CONCLUSION: This model, which mimics surgical haemorrhage, yields no evidence of a difference between colloids and crystalloids with regard to the pulmonary consequences of blood volume restoration. Functional changes in the lung should not be a key concern when choosing fluid replacement therapy with these solutions.

Lung function and exhaled nitric oxide in healthy unsedated African infants.

BACKGROUND AND OBJECTIVE: 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. METHODS: Lung function was performed on healthy South African infants enrolled in a birth cohort study, the Drakenstein child health study. Infants were excluded if they were born preterm or had a history of neonatal respiratory distress or prior respiratory tract infection. Measurements, made during natural sleep, included the forced oscillation technique, tidal breathing, exhaled nitric oxide and multiple breath washout measures. RESULTS: Three hundred sixty-three infants were tested. Acceptable and repeatable measurements were obtained in 356 (98%) and 352 (97%) infants for tidal breathing analysis and exhaled nitric oxide outcomes, 345 (95%) infants for multiple breath washout and 293 of the 333 (88%) infants for the forced oscillation technique. Age, sex and weight-for-age z score were significantly associated with lung function measures. CONCLUSIONS: This study provides reference data for unsedated infant lung function in African infants and highlights the importance of using population-specific data.

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

BACKGROUND AND OBJECTIVE: 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. METHODS: Healthy term infants were studied at 6-10 weeks of age using the forced oscillation technique. Respiratory impedance was measured in the frequency range 8-48 Hz via a face mask during natural sleep. Respiratory system resistance, compliance and inertance were calculated from the impedance spectra. RESULTS: Of 177 infants tested, successful measurements were obtained in 164 (93%). Median (25-75%) values for resistance, compliance and inertance were 50.2 (39.5-60.6) cmH2 O.s.L(-1), 0.78 (0.61-0.99) mL.cmH2 O(-1) and 0.062 (0.050-0.086) cmH2 O.s(2) .L(-1), respectively. As a group, male infants had 16% higher resistance (P = 0.006) and 18% lower compliance (P = 0.02) than females. Infants whose mothers smoked during pregnancy had a 19% lower compliance than infants not exposed to tobacco smoke during pregnancy (P = 0.005). Neither maternal HIV infection nor ethnicity had a significant effect on respiratory mechanics. CONCLUSIONS: The forced oscillation technique is sensitive enough to demonstrate the effects of tobacco smoke exposure and sex in respiratory mechanics in healthy infants. This technique will facilitate assessing perinatal influences of lung function in infancy.

Assessment of respiratory mechanics with forced oscillations in healthy newborns.

BACKGROUND: 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. METHODS: Zrs was measured during 30-s epochs of quiet sleep in term neonates born via spontaneous vaginal delivery with a non-invasive FOT between 8 and 48 Hz. Total respiratory resistance (R), compliance (C) and inertance (I) were obtained by fitting Zrs spectra. Cluster analysis was used to determine a set of minimal Zrs spectra representing optimal respiratory mechanics for each infant. RESULTS: Successful measurements were obtained in each of the first 3 days in 30/38 (78.9%) neonates. Group mean (± SD) values of R, C, I, and resonant frequency pooled for the 3 days were 45.9 ± 16.6 hPa s L(-1), 0.97 ± 0.21 ml hPa(-1), 0.082 ± 0.031 hPa s(2) L(-1) and 19.2 ± 3.2 Hz, respectively. Within-session variability represented by coefficient of variation was 5.34 ± 3.18% for R and 13.80 ± 8.57% for C. Greater between-session variability was observed for the individual infants; however, the only statistically significant change over time was a 13% increase in R from day 1 to day 2. Parameter interdependence was significant (r(2) = 0.63) between R and I reflecting the large contribution of the upper airways to the total Zrs. CONCLUSIONS: Noninvasive measurement of Zrs can be made in neonates during natural sleep with a high success rate, even in the first hours of life.

Prevention of hyperoxia-induced bronchial hyperreactivity by sildenafil and vasoactive intestinal peptide: impact of preserved lung function and structure.

OBJECTIVE: Hyperoxia exposure leads to the development of lung injury and bronchial hyperreactivity (BHR) via involvement of nitric oxide (NO) pathway. We aimed at characterizing whether the stimulation of the NO pathway by sildenafil or vasoactive intestinal peptide (VIP) is able to prevent the hyperoxia-induced development of BHR. The respective roles of the preserved lung volume and alveolar architecture, the anti-inflammatory and anti-apoptotic potentials of these treatments in the diminished lung responsiveness were also characterized. MATERIALS AND METHODS: Immature (28-day-old) rats were exposed for 72 hours to room air (Group C), hyperoxia (>95%, Group HC), or hyperoxia with the concomitant administration of vasoactive intestinal peptide (VIP, Group HV) or sildenafil (Group HS). Following exposure, the end-expiratory lung volume (EELV) was assessed plethysmographically. Airway and respiratory tissue mechanics were measured under baseline conditions and following incremental doses of methacholine to assess BHR. Inflammation was assessed by analyzing the bronchoalveolar lavage fluid (BALF), while biochemical and histological analyses were used to characterize the apoptotic and structural changes in the lungs. RESULTS: The BHR, the increased EELV, the aberrant alveolarization, and the infiltration of inflammatory cells into the BALF that developed in Group HC were all suppressed significantly by VIP or sildenafil treatment. The number of apoptotic cells increased significantly in Group HC, with no evidence of statistically significant effects on this adverse change in Groups HS and HV. CONCLUSIONS: These findings suggest that stimulating the NO pathway by sildenafil and VIP exert their beneficial effect against hyperoxia-induced BHR via preserving normal EELV, inhibiting airway inflammation and preserving the physiological lung structure, whereas the antiapoptotic potential of these treatments were not apparent in this process.

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

INTRODUCTION: The slope of phase III of the capnogram (SIII) relates to progressive emptying of the alveoli, a ventilation/perfusion mismatch, and ventilation inhomogeneity. S(III) 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. METHODS: Sidestream 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 S(III) were measured in time domain (S(T-III)) and in a smaller cohort (n = 68) by volumetry (S(V-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). RESULTS: S(T-III) and S(V-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-S(T-III) relationship, which was primarily affected by Crs. Decreases in Raw with increasing PEEP were reflected in sharp falls in S(III) in Group HC, and in moderate decreases in S(III) in Group MC, whereas S(T-III) was insensitive to changes in airway caliber in Groups LC and HL. CONCLUSIONS: SIII assessed in the time domain and by volumetry provide meaningful information about alterations in airway caliber, but only within an individual patient. Although S(T-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.

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

BACKGROUND: 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. METHODS: FOT and spirometry were performed in 20 asthmatic children (aged 5-18 years) following aerosolized histamine and methacholine at an interval of 2 weeks. The respiratory system input impedance was measured by FOT; the resistance at 6 Hz (R(6) ), the average resistance between 4 and 24 Hz, the area under the reactance curve (AX) and the resonant frequency were extracted from these recordings. Spirometry was used to obtain forced expiratory volumes and flow parameters. RESULTS: Following provocation with the two agonists, the FOT detected the airway response as early as spirometry. When the greater variability of the impedance parameters was taken into account, the two methods were observed to have similar sensitivities. Among the lung function parameters studied, AX and R(6) were the most sensitive for the demonstration of AH. CONCLUSIONS: Our findings demonstrate that FOT is as suitable as spirometry for the measurement of bronchoconstriction and thus it may be considered for the detection of AH in asthmatic children. Since its application requires minimal cooperation, this approach imposes less stress and may be particularly favorable in the diagnosis of asthma at a young age.

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.