Lung clearance index (LCI) is a sensitive marker of early lung disease in children but has not been assessed in adults. Measurement is hindered by the complexity of the equipment required. The aims ...of this study were to assess performance of a novel gas analyser (Innocor) and to use it as a clinical tool for the measurement of LCI in cystic fibrosis (CF).
LCI was measured in 48 healthy adults, 12 healthy school-age children and 33 adults with CF by performing an inert gas washout from 0.2% sulfur hexafluoride (SF6). SF6 signal:noise ratio and 10-90% rise time of Innocor were compared with a mass spectrometer used in similar studies in children.
Compared with the mass spectrometer, Innocor had a superior signal:noise ratio but a slower rise time (150 ms vs 60 ms) which may limit its use in very young children. Mean (SD) LCI in healthy adults was significantly different from that in patients with CF: 6.7 (0.4) vs 13.1 (3.8), p<0.001. Ten of the patients with CF had forced expiratory volume in 1 s > or = 80% predicted but only one had a normal LCI. LCI repeats were reproducible in all three groups of subjects (mean intra-visit coefficient of variation ranged from 3.6% to 5.4%).
Innocor can be adapted to measure LCI and affords a simpler alternative to a mass spectrometer. LCI is raised in adults with CF with normal spirometry, and may prove to be a more sensitive marker of the effects of treatment in this group.
Benralizumab is an IL5-receptor monoclonal antibody licensed for the treatment of severe eosinophilic asthma (SEA). It has demonstrated efficacy in clinical trials in reducing asthma exacerbation ...rates and maintenance oral corticosteroids (mOCSs).
What is the real-world effectiveness of benralizumab and what baseline characteristics are associated with response to therapy?
We assessed outcomes in all SEA patients who began benralizumab treatment at our specialist center. At each dosing visit, exacerbation history, mOCS dose, spirometry, and Asthma Control Questionnaire (ACQ6) and Mini-Asthma Quality of Life Questionnaire (mAQLQ) scores were recorded. Response to treatment was defined as a reduction of ≥ 50% in annualized exacerbation rate (AER) or in mOCS dose after 48 weeks of treatment. Super response was defined as zero exacerbations and no mOCSs for asthma.
One hundred thirty patients were included in the analysis. At 48 weeks, a 72.8% reduction in AER was noted, from 4.92 ± 3.35 per year in the year preceding biologic treatment to 1.34 ± 1.71 per year (P < .001), including 57 patients (43.8%) who were exacerbation-free with benralizumab. In those receiving mOCSs (n = 74 56.9%), the median daily prednisolone dose fell from 10 mg (interquartile range, 5-20 mg) to 0 mg (interquartile range, 0-5 mg; P < .001), and 38 of 74 patients (51.4%) were able to discontinue mOCS therapy. Clinically and statistically significant improvements were found in ACQ6 scores, mAQLQ scores, and FEV1. Overall, 51 patients (39%) met the super responder definition and 112 patients (86%) met the responder definition. The optimal regression model of super responders vs other responders included baseline characteristics associated with a strongly eosinophilic phenotype and less severe disease. Eighteen patients (13.8%) were nonresponders to benralizumab. Evidence of chronic airway infection was observed in 6 of 18 patients, and an increase in the blood eosinophil count consistent with the development of anti-drug antibodies was observed in 5 of 18 patients.
In a large real-world SEA cohort, benralizumab led to significant improvements in all clinical outcome measures. A lack of response was seen in a minority of patients and should be a focus for future investigation.
The forced oscillation technique (FOT) is a powerful, integrative and translational tool permitting the experimental assessment of lung function in mice in a comprehensive, detailed, precise and ...reproducible manner. It provides measurements of respiratory system mechanics through the analysis of pressure and volume signals acquired in reaction to predefined, small amplitude, oscillatory airflow waveforms, which are typically applied at the subject's airway opening. The present protocol details the steps required to adequately execute forced oscillation measurements in mice using a computer-controlled piston ventilator (flexiVent; SCIREQ Inc, Montreal, Qc, Canada). The description is divided into four parts: preparatory steps, mechanical ventilation, lung function measurements, and data analysis. It also includes details of how to assess airway responsiveness to inhaled methacholine in anesthetized mice, a common application of this technique which also extends to other outcomes and various lung pathologies. Measurements obtained in naïve mice as well as from an oxidative-stress driven model of airway damage are presented to illustrate how this tool can contribute to a better characterization and understanding of studied physiological changes or disease models as well as to applications in new research areas.
The use of the steep Trendelenburg position and abdominal CO2-insufflation during surgery can lead to significant reduction in pulmonary compliance and upper airway oedema. The postoperative time ...course of these effects and their influence on postoperative lung function is unknown. Therefore, we assessed intra- and extrathoracic airway resistance and nasal air flow in patients with or without chronic obstructive pulmonary disease (COPD) during robotic-assisted prostatectomy.
In 55 patients without and 20 patients with COPD spirometric measurements and nasal resistance were obtained before operation, 40 and 120 min, and 1 and 5 days after operation. We measured vital capacity (VC), forced expiratory volume in 1 s (FEV1), maximal mid-expiratory and inspiratory flow (MEF50, MIF50), arterial oxygen saturation, and nasal flow. The occurrence of postoperative conjunctival oedema (chemosis) was also assessed.
In patients without COPD, MEF50/MIF50 increased and nasal flow decreased significantly after surgery (P<0.0001) and normalized within 24 h. VC and FEV1 decreased after operation with a nadir at 24 h and recovered to normal until the fifth day (P<0.0001). In patients with COPD, changes in MEF50/MIF50 and nasal flow were similar, while changes in VC and FEV1 lasted beyond the fifth day (P<0.0001).
Robotic-assisted prostatectomy in the steep Trendelenburg position led to an increase in upper airway resistance directly after surgery that normalized within 24 h. The development of chemosis can be indicative of increased upper airway resistance. In patients without COPD, VC and FEV1 were reduced after surgery and recovered within 5 days, while in patients with COPD, the alteration lasted beyond 5 days.
There are numerous reference equations available for the single-breath transfer factor of the lung for carbon monoxide (
); however, it is not always clear which reference set should be used in ...clinical practice. The aim of the study was to develop the Global Lung Function Initiative (GLI) all-age reference values for
Data from 19 centres in 14 countries were collected to define
reference values. Similar to the GLI spirometry project, reference values were derived using the LMS (lambda, mu, sigma) method and the GAMLSS (generalised additive models for location, scale and shape) programme in R.12 660
measurements from asymptomatic, lifetime nonsmokers were submitted; 85% of the submitted data were from Caucasians. All data were uncorrected for haemoglobin concentration. Following adjustments for elevation above sea level, gas concentration and assumptions used for calculating the anatomic dead space volume, there was a high degree of overlap between the datasets. Reference values for Caucasians aged 5-85 years were derived for
, transfer coefficient of the lung for carbon monoxide and alveolar volume.This is the largest collection of normative
data, and the first global reference values available for
.
Respiratory rate (RR) is an important physiological parameter whose abnormality has been regarded as an important indicator of serious illness. In order to make RR monitoring simple to perform, ...reliable and accurate, many different methods have been proposed for such automatic monitoring. According to the theory of respiratory rate extraction, methods are categorized into three modalities: extracting RR from other physiological signals, RR measurement based on respiratory movements, and RR measurement based on airflow. The merits and limitations of each method are highlighted and discussed. In addition, current works are summarized to suggest key directions for the development of future RR monitoring methodologies.
Summary
Background
Obesity is highly prevalent in asthmatic children and associated with worse clinical outcomes. Energy restriction to induce weight loss in asthmatic children has not been ...investigated in a randomized controlled trial (RCT).
Objective
To assess if (1) weight loss can be achieved in obese asthmatic children using a dietary intervention; and (2) changes in asthma outcomes occur following diet‐induced weight loss.
Methods
In a 10‐week pilot RCT, obese asthmatic children, aged 8–17 years, were randomized to a wait‐list control (WLC) (n = 15) or dietary‐intervention group (DIG) (n = 13). Lung function, Asthma Control Questionnaire (ACQ) score, and sputum and systemic inflammation were assessed at baseline and post‐intervention. (Australian New Zealand Clinical Trials Registry: ACTRN12610000955011).
Results
Body mass index (BMI) z‐score reduced significantly in the DIG vs. the WLC (−0.2 −0.4, −0.1 vs. 0.0 −0.1, 0.0, P = 0.014). Expiratory reserve volume (ERV) increased significantly within the DIG, but not compared to the WLC (0.7 0.0, 1.0 L vs. 0.3 0.0, 0.8 L, P = 0.355). ACQ improved significantly in the DIG, compared to the WLC (−0.4 −0.7, 0.0 vs. 0.1 0.0, 0.6, P = 0.004). Airway and systemic inflammation did not change within the DIG. In comparison, C‐Reactive Protein (CRP) increased significantly in the WLC (−0.4 −0.5, 0.4 vs. 0.7 −0.1, 1.9, P = 0.037). Change (∆) in BMI z‐score correlated with ∆CRP (r = 0.47, P = 0.012) and ∆exhaled nitric oxide (eNO) (r = 0.46, P = 0.034), and ∆ACQ was associated with ∆CRP (r = 0.43, P = 0.029).
Conclusion and Clinical Relevance
Dietary intervention can induce acute weight loss in obese asthmatic children with subsequent improvements in static lung function and asthma control. Systemic and airway inflammation did not change following weight loss. However, changes in BMI z‐score were associated with changes in airway and systemic inflammation and this requires further investigation in a larger RCT. This is the first weight loss RCT conducted in obese asthmatic children. Diet‐induced weight loss can achieve significant improvements in clinical outcomes for obese children with asthma.
PDF
