Multiple Breath Nitrogen Washout Test Research Articles

Lung Clearance Index Improves in People with Cystic Fibrosis not Achieving a Clinical Important Difference in Forced Expiratory Volume in One Second After Elexacaftor/Tezacaftor/Ivacaftor Therapy.

In people with cystic fibrosis (pwCF), elexacaftor/tezacaftor/ivacaftor (ETI) therapy is associated with an average improvement in FEV1 of 10-14%. However, a subset of individuals fails to achieve a clinically meaningful increase in spirometric indicators. In this study, we aimed to assess whether the lung clearance index (LCI2.5), a more sensitive indicator of lung involvement, improves following ETI initiation in this population. We conducted a prospective observational study in a specialized CF center in Italy. PwCF performed a spirometry and a multiple breath nitrogen washout test the day they initiated ETI therapy and after 6 and 12months. They were grouped according to the 12-month change in FEV1 into two groups: Individuals who experienced a change in FEV1 ≥ a minimal clinically important difference (MCID) of 3% and those who did not. Mean changes in LCI2.5 were estimated using generalized estimating equations. The study included 129 pwCF who initiated ETI at our center (Age Range: 12-36years). In 20 subjects (15.5%), the FEV1 change was < MCID. These individuals had better baseline pulmonary function than those with FEV1 changes ≥ MCID (Median FEV1: 102.5 vs 87.0%), with the majority (90%) having FEV1 values ≥ 90%. Mean changes in LCI2.5 at 12-month follow-up visit were -1.44 units (95% CI: -2.12; -0.75) in individuals with changes in FEV1 < MCID and -2.64 units (95% CI: -3.05; -2.23) in those with values ≥ MCID. LCI2.5 is a useful measure to monitor the effectiveness of ETI in pwCF with normal spirometry and limited FEV1 change following treatment initiation.

Ventilation heterogeneity is increased in adults exposed to coal mine fire-related PM2.5.

The Hazelwood Health Study was set up to study long-term health effects of a mine fire that blanketed residents of the Latrobe Valley with smoke for 45 days in 2014. The Respiratory Stream specifically assessed the impact of fine particulate matter <2.5 μm diameter (PM2.5) exposure from mine fire smoke on lung health. The multiple breath nitrogen washout (MBW) test assesses ventilation heterogeneity, which may detect sub-clinical airways dysfunction not identified using standard tests such as spirometry. This analysis assessed the association of PM2.5 exposure with measures of ventilation heterogeneity. Exposed (Morwell) and unexposed (Sale) participants were recruited 3.5-4 years after the fire from those who had participated in an Adult Survey. MBW was performed to measure lung clearance index (LCI), functional residual capacity (FRC), acinar (Sacin) and conductive (Scond) ventilation heterogeneity. PM2.5 exposure was estimated with emission and chemical transport models. Multivariable linear regression models were fitted controlling for confounders. We recruited 519 participants. MBW tests were conducted on 504 participants with 479 acceptable test results (40% male; 313 exposed, 166 unexposed). Exposure to mine fire-related PM2.5 was associated with increasing Scond (β = 1.57/kL, 95%CI: 0.20-2.95, p = 0.025), which was comparable to the estimated effect on Scond of 4.7 years of aging. No other MBW outcomes were statistically different. Increasing exposure to PM2.5 was associated with increased ventilation heterogeneity in the conductive region of the lungs 4 years after the event.

Functional disorders of the respiratory system after a new coronavirus infection COVID-19

COVID-19 (Coronavirus disease 2019) is an infectious disease caused by the coronavirus SARS-CoV-2, characterized by a high level of morbidity and mortality. A new coronavirus infection affects all organs and systems and often occurs with lung damage and respiratory failure. In a significant part of patients after the acute period of COVID-19, the symptoms of the disease persist, but the most problematic symptoms are the ones regarding lung damage that persists for a long amount of time.&#x0D; This review summarizes the results of our research in 20202021. The purpose of the conducted studies was to estimate the functional parameters of the respiratory system in patients that have been infected by COVID-19. Along with conventional pulmonary function tests (spirometry, body plethysmography and diffusion test), impulse oscillometry, the multiple-breath nitrogen washout test, determination of the maximum inspiratory and expiratory pressures were performed in all patients. Thus, we evaluated the ventilation and gas exchange function of the bronchopulmonary system, the functional state of the peripheral parts of the lungs, including the small airways, the uniformity of pulmonary ventilation and the strength of the respiratory muscles in different periods of recovery after COVID-19, including the follow-up after medical rehabilitation.&#x0D; To sum up, comprehensive functional assessment of the respiratory system is an important clinical tool that allows the planning of pharmacotherapy and to create individual programs of medical rehabilitation of patients who had COVID-19.

Methods for diagnosing dysfunction of small airways and uniformity of lung ventilation: their use after a novel coronavirus infection

In this lecture, we discussed methods and approaches to the diagnosis of small airways dysfunction, such as multiple breath nitrogen washout test, impulse oscillometry, as well as the calculation of poorly communicating fraction (PCF) as the ratio of total lung capacity to alveolar volume. The detection of the small airways dysfunction with the help of the diagnostic tools listed above makes it possible to establish functional disorders of the respiratory system in the early stages of bronchopulmonary diseases, when the results of traditional pulmonary functional tests remain within normal values. Thus, a well-standardized and the most accessible method for detecting the peripheral airways dysfunction is body plethysmography, which is used to diagnose the presence of “air trappings”. However, in the early stages of bronchopulmonary diseases, the possibilities of this method are limited. The lecture focuses primarily on the results of our own researches which were performed on patients who have suffered from a novel coronavirus infection complicated by viral pneumonia. Spirometry, body plethysmography, diffusion test, impulse oscillometry, multiple breath nitrogen washout test were conducted, and PCF index was calculated in all patients included in this analysis. The description of the PCF index, the method of its calculation, the range of normal values, as well as the possibilities of application in clinical practice are given for the first time in the Russian literature. The approaches to assessing the dysfunction of the small airways described in the lecture are not widely used at present, however, we hope that the knowledge that is currently being applied in scientific laboratories will gradually be introduced into routine clinical practice.

Ventilation Heterogeneity in Asthma and COPD: The Value of the Poorly Communicating Fraction as the Ratio of Total Lung Capacity to Alveolar Volume

Background: The ventilation heterogeneity (VH) is reliably assessed by the multiple-breath nitrogen washout (MBNW), which provides indices of conductive (S_cond) and acinar (S_acin) VH as well as the lung clearance index (LCI), an index of global VH. VH can be alternatively measured by the poorly communicating fraction (PCF), that is, the ratio of total lung capacity by body plethysmography to alveolar volume from the single-breath lung diffusing capacity measurement. Objectives: Our objective was to assess VH by PCF and MBNW in patients with asthma and with COPD and to compare PCF and MBNW parameters in both patient groups. Method: We studied 35 asthmatic patients and 45 patients with COPD. Each patient performed spirometry, body plethysmography, diffusing capacity, and MBNW test. Results: Compared to COPD patients, asthmatics showed a significantly lesser degree of airflow obstruction and lung hyperinflation. In asthmatic patients, both PCF and LCI and S_acin values were significantly lower than the corresponding ones of COPD patients. In addition, in both patient groups, PCF showed a positive correlation with LCI (p < 0.05) and S_acin (p < 0.05), but not with S_cond. Lastly, COPD patients with PCF >30% were highly likely to have a value ≥2 of the mMRC dyspnea scale. Conclusions: These results showed that PCF, a readily measure derived from routine pulmonary function testing, can provide a comprehensive measure of both global and acinar VH in asthma and in COPD patients and can be considered as a comparable tool to the well-established MBNW technique.

Diagnosing ventilation inhomogeneity after COVID-19 by multiple-breath nitrogen washout test

The aimwas to evaluate the ventilation inhomogeneity (VIH) by the multiple-breath nitrogen washout test (MBNW) after COVID-19 and to identify the relationship of the lung clearance index (LCI) with other functional parameters of the respiratory system.Methods.The cross-sectional study included 35 patients (97% men); the median age was 44 years. Spirometry, body plethysmography, diffusing capacity of the lung for carbon monoxide (DLco), MBNW test, and impulse oscillometry were performed. Dyspnea was evaluated by mMRC scale. MBNW test was performed using the Easy-one Pro, MBW Module (ndd Medizintechnik AG, Switzerland).Results. The patients were divided into 2 groups. Group 1 included 21 (60%) patients who were not diagnosed with VIH. Group 2 included 14 (40%) patients with VIH. The median testing period was 72 (47 - 109) days from the onset of COVID-19. The median of the maximum volume of lung damage determined by high-resolution computed tomography (CTmax) was 50% in the acute period of the disease and 12% during the study. The medians of all analyzed parameters remained normal in the study cohort as well as in groups 1 and 2, except the resonance frequency (fres) in group 2. Statistically significant differences were found between groups 1 and 2 in the absolute frequency dependence of resistance (R5 - R20), reactance area (AX), fres. Significant differences were also found in pathological changes of vital capacity, forced expiratory volume in the first second (FEV1), (R5 - R20). The abnormalities were more common in group 2. A significant correlation was shown between LCI with the ratio of residual lung volume to total lung capacity, (R5 - R20), AX, fres, relative frequency dependence of resistance, CTmax, FEV1 and trasfer-factor (DLco).Conclusion. Seventy-two days after the onset of CoVID-19, the ventilation inhomogeneity was detected in 40% of the patients, decreased DLco- in 23%, airway obstruction - in 11.4%, and restrictive ventilatory defect - in 8.6%. Correlations were found between LCI and DLco, spirometry parameters, body plethysmography, impulse oscillometry, and CTmax.

Respiratory symptoms in smokers with normal spirometry: clinical significance and management considerations.

Current respiratory society guidelines recommend confirming the diagnosis of chronic obstructive pulmonary disease (COPD) with demonstration of airflow obstruction on spirometry. However, multiple recent studies have demonstrated that smokers without overt airflow obstruction on spirometry, termed symptomatic smokers, have evidence of structural lung disease on imaging, have a substantial symptom burden, and also suffer respiratory exacerbations. In this review, we provide an overview of the epidemiology of symptomatic smokers, and address issues of screening and diagnosis, evaluation, and management considerations. Two large prospective cohorts of adults with and at risk for COPD quantified the respiratory morbidity of symptomatic smokers. These studies demonstrated that approximately half of smokers without spirometrically defined airflow obstruction have increased respiratory symptoms, poor quality of life, low functional capacity, and suffer from respiratory exacerbations. Symptomatic smokers also have evidence of structural lung disease on imaging, and are at risk for faster lung function decline compared with those without respiratory symptoms. Several methods have been proposed to detect smoking-related lung damage among symptomatic smokers with normal forced expired volume in 1 second (FEV1)/forced vital capacity (FVC) ratio. Novel spirometry measures have been reported to diagnose disease before detection using traditional spirometry thresholds. Small airway involvement can be detected earlier using impulse oscillometry and metrics on multiple breath nitrogen washout tests. Imaging biomarkers have been developed that are associated with respiratory morbidity and lung function decline in symptomatic smokers. The translation of novel methods for COPD disease detection into more timely introduction of therapeutics and a consequent reduction in long-term morbidity and mortality has not yet been observed. A better understanding of the pathobiologic basis of disease in smokers without overt airflow limitation, and earlier recognition of lung disease, while also appropriately evaluating for comorbidities that may account for the symptoms, will enhance the management of symptomatic smokers with preserved lung function.

Residual volume/total lung capacity ratio confers limited additive significance to lung clearance index for assessment of adults with bronchiectasis

BackgroundMosaicism and hyperinflation are common pathophysiologic features of bronchiectasis. The magnitude of ventilation heterogeneity might have been affected by the degree of hyperinflation. Some studies have evaluated the discriminative performance of lung clearance index (LCI) in bronchiectasis patients, but the additive diagnostic value of hyperinflation metrics to LCI is unknown.ObjectiveTo compare LCI and the ratio of residual volume to total lung capacity (RV/TLC), along with the LCI normalized with RV/TLC, in terms of discriminative performance, correlation and concordance with clinical variables in adults with bronchiectasis.MethodsMeasurement items included chest high-resolution computed tomography, multiple-breath nitrogen washout test, spirometry, and sputum culture. We analyzed bronchodilator responses by stratifying LCI and RV/TLC according to their median levels (LCIHigh/RV/TLCHigh, LCILow/RV/TLCHigh, LCIHigh/RV/TLCLow, and LCILow/RV/TLCLow).ResultsData from 127 adults with clinically stable bronchiectasis were analyzed. LCI had greater diagnostic value than RV/TLC in discriminating moderate-to-severe from mild bronchiectasis, had greater concordance in reflecting clinical characteristics (including the number of bronchiectatic lobes, radiological severity score, and the presence of cystic bronchiectasis). Normalization of LCI with RV/TLC did not contribute to greater discriminative performance or concordance with clinical variables. The LCI, before and after normalization with RV/TLC, correlated statistically with age, sex, HRCT score, Pseudomonas aeruginosa colonization, cystic bronchiectasis, and ventilation heterogeneity (all P<0.05). Different bronchodilator responses were not significant among the four subgroups of bronchiectasis patients, including those with discordant LCI and RV/TLC levels.ConclusionLCI is superior to RV/TLC for bronchiectasis assessment. Normalization with RV/TLC is not required. Stratification of LCI and RV/TLC is not associated with significantly different bronchodilator responses.

A Systematic Approach to Multiple Breath Nitrogen Washout Test Quality.

BackgroundAccurate estimates of multiple breath washout (MBW) outcomes require correct operation of the device, appropriate distraction of the subject to ensure they breathe in a manner representative of their relaxed tidal breathing pattern, and appropriate interpretation of the acquired data. Based on available recommendations for an acceptable MBW test, we aimed to develop a protocol to systematically evaluate MBW measurements based on these criteria.Methods50 MBW test occasions were systematically reviewed for technical elements and whether the breathing pattern was representative of relaxed tidal breathing by an experienced MBW operator. The impact of qualitative and quantitative criteria on inter-observer agreement was assessed across eight MBW operators (n = 20 test occasions, compared using a Kappa statistic).ResultsUsing qualitative criteria, 46/168 trials were rejected: 16.6% were technically unacceptable and 10.7% were excluded due to inappropriate breathing pattern. Reviewer agreement was good using qualitative criteria and further improved with quantitative criteria from (κ = 0.53–0.83%) to (κ 0.73–0.97%), but at the cost of exclusion of further test occasions in this retrospective data analysis.ConclusionsThe application of the systematic review improved inter-observer agreement but did not affect reported MBW outcomes.

Maximal mid-expiratory flow is a surrogate marker of lung clearance index for assessment of adults with bronchiectasis.

Little is known about the comparative diagnostic value of lung clearance index (LCI) and maximal mid-expiratory flow (MMEF) in bronchiectasis. We compared the diagnostic performance, correlation and concordance with clinical variables, and changes of LCI and MMEF% predicted during bronchiectasis exacerbations (BEs). Patients with stable bronchiectasis underwent history inquiry, chest high-resolution computed tomography (HRCT), multiple-breath nitrogen wash-out test, spirometry and sputum culture. Patients who experienced BEs underwent these measurements during onset of BEs and 1 week following antibiotics therapy. Sensitivity analyses were performed in mild, moderate and severe bronchiectasis. We recruited 110 bronchiectasis patients between March 2014 and September 2015. LCI demonstrated similar diagnostic value with MMEF% predicted in discriminating moderate-to-severe from mild bronchiectasis. LCI negatively correlated with MMEF% predicted. Both parameters had similar concordance in reflecting clinical characteristics of bronchiectasis and correlated significantly with forced expiratory flow in one second, age, HRCT score, Pseudomonas aeruginosa colonization, cystic bronchiectasis, ventilation heterogeneity and bilateral bronchiectasis. In exacerbation cohort (n = 22), changes in LCI and MMEF% predicted were equally minimal during BEs and following antibiotics therapy. In sensitivity analyses, both parameters had similar diagnostic value and correlation with clinical variables. MMEF% predicted is a surrogate of LCI for assessing bronchiectasis severity.

Long-term effects of metaproterenol in asthmatic children.

Oral metaproterenol was administered daily for 3 months to asthmatic children. The study was designed to determine whether chronic tolerance developed to this drug. Initial and final crossovers on the first 2 and the last 2 days of the investigation to a test dose of metaproterenol and placebo failed to show tolerance as indicated by improvement in lung volumes and dynamic mechanics of breathing after metaproterenol. Forced expiratory volume in 1 sec was the test most consistent in demonstrating bronchodilation; the action of metaproterenol. Forced expiratory volume in 1 sec was the test most consistent in demonstrating bronchodilation; the action of metaproterenol appeared to last at least 5 hours as measured by this test. T of distribution of ventilation, e.g., single- and multiple-breath nitrogen washout tests, were not consistently altered by metaproterenol. These tests did not appear to be sufficiently sensitive to detect improvement even when airway resistance decreased and forced expiratory volume in 1 sec increased toward the normal range.

Ultrafine Particles from Traffic Emissions and Children's Health (UPTECH) in Brisbane, Queensland (Australia): study design and implementation.

Ultrafine particles are particles that are less than 0.1 micrometres (µm) in diameter. Due to their very small size they can penetrate deep into the lungs, and potentially cause more damage than larger particles. The Ultrafine Particles from Traffic Emissions and Children’s Health (UPTECH) study is the first Australian epidemiological study to assess the health effects of ultrafine particles on children’s health in general and peripheral airways in particular. The study is being conducted in Brisbane, Australia. Continuous indoor and outdoor air pollution monitoring was conducted within each of the twenty five participating school campuses to measure particulate matter, including in the ultrafine size range, and gases. Respiratory health effects were evaluated by conducting the following tests on participating children at each school: spirometry, forced oscillation technique (FOT) and multiple breath nitrogen washout test (MBNW) (to assess airway function), fraction of exhaled nitric oxide (FeNO, to assess airway inflammation), blood cotinine levels (to assess exposure to second-hand tobacco smoke), and serum C-reactive protein (CRP) levels (to measure systemic inflammation). A pilot study was conducted prior to commencing the main study to assess the feasibility and reliably of measurement of some of the clinical tests that have been proposed for the main study. Air pollutant exposure measurements were not included in the pilot study.

Automated detection of the phase III slope during inert gas washout testing

We describe a method to determine the phase III slope for the purpose of calculating indexes of ventilation heterogeneity, S(acin) and S(cond), from the multiple breath nitrogen washout test (MBNW). Our automated method applies a recursive, segmented linear regression technique to each breath of the MBNW test and determines the best point of transition, or breakpoint, between each phase of the washout. A sample set of 50 MBNW tests (controls, asthma, and COPD) was used to establish the conditions in which the phase III slope obtained from the automated technique best matched that obtained by two manual interpreters. We then applied our technique to a test set of 30 subjects (with an even number of subjects in each of the above groups) and compared these results against the manual analysis of a third independent manual interpreter. Indexes of ventilation heterogeneity were determined using both methods and compared. The phase III slopes determined by the automatic technique best matched the manual interpreter when the phase III slope was calculated from the phase II-III transition point plus the addition of 50% of the phase II volume to the end of the expiration. Calculation of the indexes S(acin) and S(cond) showed no overall difference between analysis methods in either S(acin) (P = 0.14) or S(cond) (P = 0.59) when the set threshold was applied to our automated analysis. Our analysis method provides an alternate means for rapid quantification of the MBNW test, removing operator dependence without alteration in either S(acin) or S(cond).

Impaired gas mixing and low lung volume in preterm infants with mild chronic lung disease.

The aim of this study was to assess the possible role of gas mixing inefficiency in spontaneously breathing infants with mild chronic lung disease (CLD) of prematurity in relation to changes in other functional parameters. A simple bedside technique for recording and analysis of multiple breath nitrogen washout curves was applied together with occlusion mechanics. Fifteen preterm infants with mild or moderately severe CLD were studied at a mean postconceptional age of 35 wk, together with 15 healthy preterm infants at the same maturity. All infants breathed spontaneously, and the test was performed by a continuous bypass flow system, connected to a face mask, a pneumotachograph, and a nitrogen meter. The results showed impaired gas mixing with moment ratios above the 95th percentile of the normal group in 11/15 infants with CLD. Functional residual capacity (FRC) was low in 13/15 infants, but specific compliance and resistance of the respiratory system did not differ between the groups. As FRC and moment ratios were not correlated, it is suggested that they may reflect different aspects of the pathophysiology in CLD. It is concluded that low FRC and disturbed gas mixing are characteristic disturbances in CLD at different degrees of severity. The multiple breath nitrogen washout test, followed by moment analysis of end-tidal nitrogen concentrations, is a simple and sensitive method for detection of these disturbances and for monitoring purposes.