Single-breath Nitrogen Washout Research Articles

Single and multiple breath nitrogen washout compared with the methacholine test in patients with suspected asthma and normal spirometry

BackgroundMethods used to assess ventilation heterogeneity through inert gas washout have been standardised and showed high sensitivity in diagnosing many respiratory diseases. We hypothesised that nitrogen single or multiple breath...

Association between clinical, serological, functional and radiological findings and ventilatory distribution heterogeneity in patients with rheumatoid arthritis.

In rheumatoid arthritis (RA), the involvement of the pulmonary interstitium can lead to structural changes in the small airways and alveoli, leading to reduced airflow and maldistribution of ventilation. The single-breath nitrogen washout (SBN2W) test is a measure of the ventilatory distribution heterogeneity and evaluates the small airways. This study aimed to find out which clinical, serological, functional and radiological findings are useful to identify RA patients with pathological values of the phase III slope (SIII) measured by the SBN2W test. This was a cross-sectional study in which RA patients were assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI) and the Clinical Disease Activity Index (CDAI) and underwent serological analysis of autoantibodies and inflammatory markers. In addition, they underwent pulmonary function tests (including the SBN2W test) and chest computed tomography (CT). Of the 60 RA patients evaluated, 39 (65%) had an SIII >120% of the predicted value. There were significant correlations between SIII and age (r = 0.56, p<0.0001), HAQ-DI (r = 0.34, p = 0.008), forced vital capacity (FVC, r = -0.67, p<0.0001), total lung capacity (r = -0.46, p = 0.0002), residual volume/total lung capacity (TLC) (r = 0.44, p = 0.0004), and diffusing capacity of the lungs for carbon monoxide (r = -0.45, p = 0.0003). On CT scans, the subgroup with moderate/severe disease had a significantly higher SIII than the normal/minimal/mild subgroup (662 (267-970) vs. 152 (88-283)% predicted, p = 0.0004). In the final multiple regression model, FVC, extent of moderate/severe involvement and age were associated with SIII, explaining 59% of its variability. In patients with RA, FVC, extent of lung involvement and age, all of which are easily obtained variables in clinical practice, identify poorly distributed ventilation. In addition, the presence of respiratory symptoms and deteriorated physical function are closely related to the distribution of ventilation in these patients.

Assessing the relationship between cardiovascular and small airway disease and acute events in COPD: The ARCADIA study protocol

The initial alterations of chronic obstructive pulmonary disease (COPD) involve the small airways. Small airway disease (SAD) is related to lung hyperinflation and air trapping. Several lung function tests may detect the presence of SAD, namely forced mid-expiratory flows, residual volume (RV), RV/total lung capacity (TLC) ratio, functional residual capacity, airway resistances obtained with body-plethysmography and oscillometry, and the single-breath nitrogen washout test. Additionally, high-resolution computed tomography can detect SAD. In addition to SAD, COPD is related to cardiovascular disease (CVD) such as heart failure, peripheral vascular disease, and ischemic heart disease. No studies have assessed the relationship between CVD, COPD, and SAD. Therefore, the main objective of the Assessing the Relationship between Cardiovascular and small Airway Disease and Acute events in COPD (ARCADIA) study is to assess the risk of CVD in COPD patients according to SAD in a real-life setting. The correlation between CVD, mortality, and acute exacerbation of COPD (AECOPD) is also evaluated.ARCADIA is a 52-week prospective, multicentre, pilot, observational, cohort study conducted in ≥22 pulmonary centres in Italy and that enrols ≥500 COPD patients, regardless of disease severity (protocol registration: ISRCTN49392136). SAD is evaluated at baseline, after that CVD, mortality, and AECOPD are recorded at 6 and 12 months. Bayesian inference is used to quantify the risk and correlation of the investigated outcomes in COPD patients according to SAD.The ARCADIA study provides relevant findings in the daily clinical management of COPD patients.

Comparison of pulmonary and small airways function between idiopathic inflammatory myopathies patients with and without interstitial lung disease.

To evaluate pulmonary and small airway function in patients with idiopathic inflammatory myopathies (IIM) and make comparisons between patients with and without interstitial lung disease (ILD). Newly diagnosed IIM patients with and without ILD determined by high resolution computed tomography were included in the study. Pulmonary and small airway function was assessed by spirometry, diffusing capacity for carbon monoxide (DLCO), body plethysmography, single and multiple breath nitrogen washout, impulse oscillometry and measurement of respiratory resistance by the interrupter technique (Rint) using the Q-box system. We used discrepancies between lung volumes measured by multiple breath nitrogen washout and body plethysmography to evaluate for small airway dysfunction. Study cohort comprised of 26 IIM patients, 13 with and 13 without ILD. IIM-ILD patients presented more frequently with dyspnoea, fever, arthralgias and positive anti-synthetase antibodies, compared to IIM patients without ILD. Classic spirometric parameters and most lung physiology parameters assessing small airway function did not differ between the two groups. Predicted total lung capacity and residual volume (TLCN2WO, RVN2WO) measured by multiple breath nitrogen washout and the TLCN2WO/TLCpleth ratio were significantly lower in IIM-ILD patients compared to those without ILD (mean: 111.1% vs. 153.4%, p=0.034, median: 171% vs. 210%, p=0.039 and median: 1.28 vs. 1.45, p=0.039, respectively). Rint tended to be higher among IIM-ILD patients (mean:100.5% vs. 76.6%, p=0.053). Discrepancies between lung volumes measured by multiple breath nitrogen washout and body plethysmography in IIM-ILD patients indicate an early small airways dysfunction in these patients.

Airspace Dimension Assessment for early detection of lung function impairment in the peripheral airways of firefighters.

Firefighters have increased risk of chronic respiratory disease. Standard clinical techniques used in medical checkups may not detect the earliest microstructural changes in peripheral airways. A new technique called Airspace Dimension Assessment (AiDA) has been shown to enable early detection of emphysema in COPD. This method may be useful in the occupational setting to detect early pulmonary changes and enable prevention. The aim of the present study was to evaluate whether AiDA detects changes in the most peripheral airways of firefighters. AiDA, measuring the effective airspace radius (r AiDA) and zero-second recovery (R 0), was used as a complement to other standardised lung function measures in 21 male firefighters and 16 age-matched male controls. There were significant differences in r AiDA and R 0 between firefighters (mean±sd r AiDA 0.301±0.024 mm; mean±sd R 0 0.336±0.116 arbitrary units) and controls (mean±sd r AiDA 0.276±0.044 mm; mean±sd R 0 0.5760.168 arbitrary units), p=0.03 and p<0.001, respectively. Higher forced vital capacity was found in firefighters (mean 101% of predicted) than in controls (mean 93% of predicted; p=0.03). No significant differences were found with regard to either the ratio between forced expiratory volume in 1 s and forced vital capacity or forced expiratory volume in 1 s. The majority of firefighters had diffusing capacity of the lung for carbon monoxide, oscillometry and single-breath nitrogen washout values within the normal ranges. AiDA parameters can provide information on early pulmonary peripheral changes that may not be seen with standard techniques used in screening of pulmonary function.

Small airways dysfunction in patients with systemic sclerosis and interstitial lung disease.

A number of studies report small airways involvement in patients with systemic sclerosis (SSc). Furthermore, small airways dysfunction is increasingly recognized in patients with interstitial lung disease (ILD) of idiopathic or autoimmune etiology. The objectives of this study were to evaluate small airways function in SSc patients with ILD and explore the effect of treatment on small airways function by using conventional and contemporary pulmonary function tests (PFTs). This single-center, prospective, observational study included a total of 35 SSc patients, with and without ILD based on HRCT scan, evaluated by a special radiologist blindly. Clinical data were collected from all patients who were also assessed for HRCT findings of small airways disease. Small airways function was assessed by classic spirometry, measurement of diffusing capacity for carbon monoxide, body plethysmography, single breath nitrogen washout (N2SBW) and impulse oscillometry (IOS). The prevalence of small airways dysfunction according to R5-R20, phase III slopeN2SBW and CV/VC methodologies was calculated in the total SSc population. Pulmonary function tests were compared between: (a) SSc-ILD and non-ILD patients and (b) two time points (baseline and follow up visit) in a subset of SSc-ILD patients who received treatment for ILD and were re-evaluated at a follow up visit after 12 months. Phase III slopeN2SBW and R5-R20 showed the highest diagnostic performance for detecting small airways dysfunction among SSc patients (61 and 37.5%, respectively). Twenty three SSc patients were found with ILD and 14 of them had a 12-month follow up visit. SSc-ILD patients compared to those without ILD exhibited increased phase III slopeN2SBW ≥120% (p = 0.04), R5-R20 ≥0.07 kPa/L/s (p = 0.025), airway resistance (Raw) (p = 0.011), and special airway resistance (sRaw) (p = 0.02), and decreased specific airway conductance (sGaw) (p = 0.022), suggesting impaired small airways function in the SSc-ILD group. Radiographic features of SAD on HRCT were observed in 22% of SSc-ILD patients and in none of SSc-non-ILD patients. Comparison of PFTs between baseline and follow-up visit after 12 months in the 14 SSc-ILD treated patients, showed improvement of phase III slopeN2SBW (p = 0.034), R5-R20 (p = 0.035) and Raw (p = 0.044) but not sRaw and sGaw parameters. Phase III slopeN2SBW and R5-R20 may reveal small airways dysfunction in SSc associated ILD before structural damage and may be partially improved in a subset of patients receiving treatment for ILD.

Prediction of COPD by the single-breath nitrogen test and various respiratory symptoms.

Early identification of subjects running an increased risk of contracting COPD enables focus on individual preventive measures. The slope of the alveolar plateau of the single-breath nitrogen washout test (N2-slope) is a sensitive measure of small-airway dysfunction. However, its role remains unexplored in predicting hospital admission or death related to COPD, i.e. incident COPD events, in relation to the presence of various respiratory symptoms.A random population sample of 625 men, aged 50 (n=218) or 60 years (n=407), was followed for 38 years for incident COPD events. At baseline, a questionnaire on respiratory symptoms and smoking habits was collected, spirometry and the single-breath nitrogen test were performed, and the N2-slope was determined. Proportional hazard regression (Cox regression) analysis was used for the prediction model.The N2-slope improved the prediction of COPD events significantly beyond that of respiratory symptoms weighted all together and other covariates (hazard ratio 1.63, 95% CI 1.20–2.22; p<0.005), a prediction applicable to subjects without (p=0.001) and with (p<0.05) airway obstruction. Dyspnoea and wheezing were the most predictive symptoms. The combination of the N2-slope and number of respiratory symptoms notably resulted in an effective prediction of incident COPD events even in nonobstructive subjects, as evidenced by a predicted incidence of ∼70% and ∼90% for a very steep N2-slope combined with many respiratory symptoms in subject without and with airway obstruction, respectively.The alveolar N2-slope should be considered in the critical need for further research on early diagnosis of COPD.

Current smoking alters phospholipid- and surfactant protein A levels in small airway lining fluid: An explorative study on exhaled breath.

Small airways are difficult to access. Exhaled droplets, also referred to as particles, provide a sample of small airway lining fluid and may reflect inflammatory responses. We aimed to explore the effect of smoking on the composition and number of exhaled particles in a smoker-enriched study population. We collected and chemically analyzed exhaled particles from 102 subjects (29 never smokers, 36 former smokers and 37 current smokers) aged 39 to 83 years (median 63). A breathing maneuver maximized the number exhaled particles, which were quantified with a particle counter. The contents of surfactant protein A and albumin in exhaled particles was quantified with immunoassays and the contents of the phospholipids dipalmitoyl- and palmitoyl-oleoyl- phosphatidylcholine with mass spectrometry. Subjects also performed spirometry and nitrogen single breath washout. Associations between smoking status and the distribution of contents in exhaled particles and particle number concentration were tested with quantile regression, after adjusting for potential confounders. Current smokers, compared to never smokers, had higher number exhaled particles and more surfactant protein A in the particles. The magnitude of the effects of current smoking varied along the distribution of each PEx-variable. Among subjects with normal lung function, phospholipid levels were elevated in current smokers, in comparison to no effect of smoking on these lipids at abnormal lung function. Smoking increased exhaled number of particles and the contents of lipids and surfactant protein A in the particles. These findings might reflect early inflammatory responses to smoking in small airway lining fluid, also when lung function is within normal limits.

Closing volume detection by single-breath gas washout and forced oscillation technique.

Closing volume (CV) is commonly measured by single-breath nitrogen washout (CVSBW). A method based on the forced oscillation technique was recently introduced to detect a surrogate CV (CVFOT). As the two approaches are based on different physiological mechanisms, we aim to investigate CVFOT and CVSBW relationship at different degrees and patterns of airway obstruction. A mathematical model was developed to evaluate the CVSBW and CVFOT sensitivity to different patterns of airway obstruction, either located in a specific lung region or equally distributed throughout the lung. The two CVs were also assessed during slow vital capacity (VC) maneuvers in triplicate in 13 healthy subjects and pre- and postmethacholine challenge (Mch) in 12 subjects with mild-moderate asthma. Model simulations suggest that CVSBW is more sensitive than CVFOT to the presence of few flow-limited or closed airways that modify the contribution of tracer-poor and tracer-rich lung regions to the overall exhaled gas. Conversely, CVFOT occurs only when at least ∼65% of lung units are flow limited or closed, regardless of their regional distribution. CVSBW did not differ between healthy subjects and those with asthma (17 ± 9% VC vs. 22 ± 10% VC), whereas CVFOT did (16 ± 5% VC vs. 23 ± 6% VC, P < 0.01). In patients with asthma, both CVSBW and CVFOT increased post-Mch (33 ± 7% VC P < 0.001 and 43 ± 12% VC P < 0.001, respectively). CVSBW weakly correlated with CVFOT (r = 0.45, P < 0.01). The closing capacities (CV+residual volume) were correlated (r = 0.74, P < 0.001), but the changes with Mch in both CVs and closing capacities did not correlate. CVFOT is easy to measure and provides a reproducible parameter useful for describing airway impairment in obstructive respiratory diseases.NEW & NOTEWORTHY The forced oscillation technique can identify a surrogate of closing volume (CVFOT). We investigated its relationship with the one measured by single-breath washout (CVSBW). CVFOT weakly correlates with CVSBW. The respective closing capacities were correlated, but their increases after methacholine challenge in asthmatics did not. Our results suggest that CVFOT is less sensitive than CVSBW to few flow-limited/closed airways but more specific in detecting increases in flow-limited/closed airways involving the majority of the lung.

Abnormal Lung Clearance Index in Cystic Fibrosis Children with Normal FEV1 and Single-Breath Nitrogen Washout Test.

Single- and multiple-breath washout tests (SBW and MBW) measure ventilation inhomogeneity, but the relationship between them is unclear. Forty-three subjects with cystic fibrosis (CF) and healthy controls (HC) 8-21years of age were recruited (CF = 30 and HC = 13) and performed nitrogen MBW, vital capacity SBW, spirometry, and plethysmography. Mean phase III slope from SBW (SIII) and lung clearance index (LCI) were significantly different between CF and HC (p = 0.017 and p < 0.0001, respectively). Based on Pearson correlation, SIII and LCI showed strong correlation (ρ = 0.81, p < 0.0001). Both SIII and LCI significantly correlated with spirometry (all p < 0.05). Among CF subjects with normal FEV1 (≥ 80%; n = 17), 76% (n = 13) had normal SIII but abnormal LCI. We conclude that LCI can be abnormal despite normal SIII and FEV1 in CF children. Although LCI and SIII showed strong correlation, our results suggest that LCI is a better test to detect ventilation inhomogeneity in CF children with normal FEV1.

Predictors of functional capacity as measured by the Glittre activities of daily living test in women with rheumatoid arthritis.

Although pulmonary involvement is the most common extra-articular manifestation of rheumatoid arthritis (RA), traditional pulmonary function tests (PFTs) do not show a good correlation with the field tests usually performed in these patients. In recent decades, measurement of ventilation distribution heterogeneity through the nitrogen single-breath washout (N2SBW) test and evaluation of functional capacity during exercise using the Glittre activities of daily living test (GA-T) have been increasingly used. Therefore, the objective of this study was to evaluate predictors of GA-T outcomes in women with RA considering demographic, anthropometric, clinical, functional variables, and chest computed tomography (CT) findings. Forty-three women with RA underwent the GA-T, the N2SBW test, spirometry, measurement of the diffusing capacity for carbon monoxide (DLco), measurement of respiratory muscle strength, and evaluation of physical function of the lower and upper limbs through the Health Assessment Questionnaire Disability Index (HAQ-DI). Chest CT scans were analyzed retrospectively. The GA-T time showed significant correlations with the DLco (rs=-0.397, P=0.008), forced vital capacity/DLco (rs=0.307, P=0.044), phase III slope of the N2SBW test (SIIIN2, rs=0.644, P<0.0001), and the HAQ-DI (rs=0.482, P=0.001). Disease extent as assessed by chest CT was associated with the GA-T time. On multiple regression analysis, the SIIIN2 and HAQ-DI were the only predictors of the GA-T time, explaining 40% of its variability. Thus, ventilation distribution heterogeneity and worse physical function substantially explain the variability in GA-T time in women with RA and varying extents of disease on chest CT.

Lung Function of Adults Born at Very Low Birth Weight

J Yang, RA Kingsford, J Horwood. Pediatrics. 2020;145(2):e20192359 To assess the lung function in adults who were very low birth weight (VLBW) infants in comparison with controls and to assess if bronchopulmonary dysplasia (BPD) added further insult to their underlying pulmonary function. The study population consisted of 226 adults, aged 26 to 30 years, selected from the 1986 New Zealand VLBW cohort (birth weight <1500 g). One hundred adults born at term in 1986 who did not require NICU admission served as age-matched controls. In this retrospective cohort analysis, participants …

Evaluation of the Small Airways in Patients with Chronic Obstructive Pulmonary Disease and Alpha-1 Antitrypsin Deficiency.

IntroductionSmall airways are not evaluated with traditional pulmonary function tests. The aim of this study was to evaluate the small airways in patients with chronic obstructive pulmonary disease (COPD) with a nitrogen washout test and to verify whether there is a difference between patients with COPD due to smoking and those with COPD due to alpha-1 antitrypsin mutation.MethodsSixteen patients with mutation in the SERPINA1 gene and 45 patients with no mutation were included in this cross-sectional study. All pulmonary function tests, including the single breath nitrogen washout test, were performed for all patients and alpha-1 antitrypsin dosage was assessed with immunonephelometry.ResultsA comparison of patients with COPD due to smoking and those with COPD due to smoking and mutation revealed a significant difference in closure volume (%), which was the poorest in the mutation group. In the group with COPD and mutation, there was an inverse correlation between smoking and closure volume (%). We also verified that similar to forced expiratory volume in the first second (FEV1), the phase III slope (%) and ΔN2 750–1250 mL (%) could be used to differentiate the severity of airflow limitation.ConclusionOur results suggest that both variables, phase III slope and the ΔN2 750–1250 mL (%), could be related to COPD severity. Therefore, alterations at the distribution of the location of the emphysema could alter the results of closer volume and that the nitrogen washout test is more sensitive when compared to traditional pulmonary function test in evaluating COPD patients.

Restrictive spirometric pattern and true pulmonary restriction in a general population sample aged 50 - 64 years

BackgroundThere is low diagnostic accuracy of the proxy restrictive spirometric pattern (RSP) to identify true pulmonary restriction. This knowledge is based on patients referred for spirometry and total lung volume determination by plethysmograpy, single breath nitrogen washout technique or gas dilution and selected controls. There is, however, a lack of data from general populations analyzing whether RSP is a valid proxy for true pulmonary restriction. We have validated RSP in relation to true pulmonary restriction in a general population where we have access to measurements of total lung capacity (TLC) and spirometry.MethodsThe data was from the Swedish CArdioPulmonary bioImage Study (SCAPIS Pilot), a general population-based study, comprising 983 adults aged 50–64. All subjects answered a respiratory questionnaire. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained before and after bronchodilation. TLC and residual volume (RV) was recorded using a body plethysmograph. All lung function values are generally expressed as percent predicted (% predicted) or in relation to lower limits of normal (LLN). True pulmonary restriction was defined as TLC < LLN5 defined as a Z score < − 1.645, i e the fifth percentile. RSP was defined as FEV1/FVC ≥ LLN and FVC < LLN after bronchodilation. Specificity, sensitivity, positive and negative likelihood ratios were calculated, and 95% confidence intervals (CIs) were calculated.ResultsThe prevalence of true pulmonary restriction was 5.4%, and the prevalence of RSP was 3.4%. The sensitivity of RSP to identify true pulmonary restriction was 0.34 (0.20–0.46), the corresponding specificity was 0.98 (0.97–0.99), and the positive likelihood ratio was 21.1 (11.3–39.4) and the negative likelihood ratio was 0.67 (0.55–0.81).ConclusionsRSP has low accuracy for identifying true pulmonary restriction. The results support previous observations that RSP is useful for ruling out true pulmonary restriction.

Lung Function of Adults Born at Very Low Birth Weight.

Much remains unknown about the consequences of very low birth weight (VLBW) and bronchopulmonary dysplasia (BPD) on adult lungs. We hypothesized that VLBW adults would have impaired lung function compared with controls, and those with a history of BPD would have worse lung function than those without. At age 26 to 30 years, 226 VLBW survivors of the New Zealand VLBW cohort and 100 term controls born in 1986 underwent lung function tests including spirometry, plethysmographic lung volumes, diffusing capacity of the lung for carbon monoxide, and single-breath nitrogen washout (SBN2). An obstructive spirometry pattern was identified in 35% VLBW subjects versus 14% controls, with the majority showing mild obstruction. Compared with controls, VLBW survivors demonstrated significantly lower forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity (FVC) ratio (FEV1/FVC), forced expiratory flow at 25% to 75% of FVC and higher residual volume (RV), RV/total lung capacity (TLC) ratio (RV/TLC), decreased diffusing capacity of the lung for carbon monoxide, and increased phase III slope for SBN2. The differences persisted after adjustment for sex and smoking status. Within the VLBW group, subjects with BPD showed significant reduction in FEV1, FEV1/FVC, and forced expiratory flow at 25% to 75% of FVC, and increase in RV, RV/TLC, and phase III slope for SBN2, versus subjects without. The differences remained after adjustment for confounders. Adult VLBW survivors showed a higher incidence of airflow obstruction, gas trapping, reduced gas exchange, and increased ventilatory inhomogeneity versus controls. The findings suggest pulmonary effects due to VLBW persist into adulthood, and BPD is a further insult on small airway function.

Ventilation distribution as a contributor to the functional exercise capacity in patients with systemic sclerosis-associated interstitial lung disease without pulmonary hypertension.

Phenotypic differences have been described between patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) and SSc-associated pulmonary hypertension, including performance differences in the 6-min walk test (6MWT). Moreover, the correlations between the 6MWT and traditional pulmonary function tests (PFTs) are weak, indicating the need to search for new parameters that explain exercise performance. Thus, our objective was to evaluate the impact of ventilation distribution heterogeneity assessed by the nitrogen single-breath washout (N2SBW) test and peripheral muscle dysfunction on the exercise capacity in patients with SSc-ILD and limited involvement of the pulmonary parenchyma. In this cross-sectional study, 20 women with SSc-ILD and 20 matched controls underwent PFTs (including spirometry, diffusing capacity for carbon monoxide (DLco), and the N2SBW test) and performed the 6MWT and knee isometric dynamometry. The 6-min walking distance (6MWD, % predicted) was strongly correlated with the phase III slope of the single-breath nitrogen washout (phase III slopeN2SBW) (r=−0.753, P<0.0001) and reasonably correlated with the forced vital capacity (FVC) (r=0.466, P=0.008) and DLco (r=0.398, P=0.011). The peripheral oxygen saturation (SpO2) during exercise was not significantly correlated with any of the pulmonary or muscle function parameters. The phase III slopeN2SBW was the only predictive variable for the 6MWD, whereas quadriceps strength and FVC/DLco were predictive variables for SpO2. Ventilation distribution heterogeneity is one factor that contributes to a lower 6MWD in SSc-ILD patients. In addition, muscle dysfunction and abnormal lung diffusion at least partly explain the decreased SpO2 of these patients.

Effects of bronchodilation on biomarkers of peripheral airway inflammation in COPD

Peripheral airway inflammation and dysfunction are key elements in the pathogenesis of COPD. The exhaled alveolar fraction of nitric oxide (CANO) is an indirect biomarker of lung peripheral inflammation. We tested whether inhaled long-acting bronchodilators (LABA) can affect CANO and we evaluated correlations with lung mechanics in patients with COPD.Two-centre, randomised, double blind, crossover study including COPD patients with moderate-to-severe airflow obstruction. Following a pharmacological washout, multi-flow exhaled fraction of NO (FENO), plethysmography, lung diffusion (DLCO), single breath nitrogen washout test and dyspnoea were measured in a crossover manner at baseline and 30, 60 and 180 min following administration of salmeterol (Sal) or formoterol fumarate (FF). (ClinicalTrials.gov, number NCT01853787).Fort-five patients were enrolled (median age: 71.8 years; 84.4% males). At baseline, CANO correlated with airway resistances (r = 0.422), residual volume/total lung capacity (RV/TLC; r = 0.375), transfer factor (r= -0.463) and forced expiratory volume in 1 s (FEV1; r= -0.375, all P < 0.01). After LABA administration, we found a significant reduction of FENO that reached statistical significance at 180’; no difference was found between FF and S. Consistently, a significant reduction of CANO was documented at 60’ and 180’ compared to baseline for both FF and S (P < 0.01 and P < 0.05, respectively). Changes in CANO were correlated with changes in vital capacity (r=-44; P < 0.001) and RV/TLC (r = 0.56; P < 0.001), but not FEV1.In COPD, direct correlations were found between the levels of CANO and the magnitude of peripheral airway dysfunction. LABA reduced CANO levels. The reduction was associated with improvement in functional parameters reflecting air trapping.

Impulse oscillometry and nitrogen washout test in the assessment of small airway dysfunction in asthma: Correlation with quantitative computed tomography

ABSTRACTObjective. Small airway dysfunction (SAD) and airway remodeling influence the disease control and progression in asthma. We investigated whether impulse oscillometry (IOS) and single breath nitrogen washout (SBN2W) could be reliable tests in evaluating SAD and airway remodeling by correlating their data with radiological parameters derived from quantitative chest multidetector computed tomography (MDCT) imaging. Methods. Lung function tests were performed before and after bronchodilator. The MDCT lung scans were acquired at full inspiration and expiration using a portable spirometer to control the respiratory manoeuvres. Symptom control was assessed using the Asthma Control Test (ACT) questionnaire. Results. Twenty six patients were enrolled. The bronchial lumen area (LA) measured with MDCT lung scan, correlated inversely with airway resistance (Raw, p < 0.001) and with total and large airway oscillometric resistance (R5, p = 0.002 and R20, p = 0.006, respectively). However these two last correlations became non-significant after Bonferroni correction for multiple comparisons. The radiological quantification of air trapping correlated with Raw (p < 0.001), residual volume (RV, p < 0.001), and the slope of phase III of SBN2W (DeltaN2, p < 0.001) whereas the correlation with small airway oscillometric resistance (R5-20) was non-significant after Bonferroni adjustment. Finally, air trapping was significantly higher in patients with a fixed bronchial obstruction in comparison to patients with reversible obstruction. Conclusions. Plethysmographic method remains the main tool to investigate SAD and airway remodeling in asthmatic patients. The integration with the SBN2W test proved useful to better evaluate the small airway involvement whereas IOS showed a weaker correlation with both radiological and clinical data.

Nitrogen single-breath washout test for evaluating exercise tolerance and quality of life in patients with chronic obstructive pulmonary disease

Pulmonary function tests (PFTs) traditionally used in clinical practice do not accurately predict exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to assess whether the nitrogen single-breath washout (N2SBW) test explains exercise intolerance and poor quality of life in stable COPD patients. This cross-sectional study included 31 patients with COPD subjected to PFTs (including the N2SBW test) and a cardiopulmonary exercise test (CPET). Patients were also evaluated using the following questionnaires: the COPD assessment test (CAT), the 36-Item Short Form Health Survey (SF36) and St. George's Respiratory Questionnaire (SGRQ). Peak oxygen uptake (peak VO2) was negatively correlated with the phase III slope of the N2SBW (SIIIN2) (r=-0.681, P<0.0001) and positively correlated with forced expiratory volume in one second (FEV1; r=0.441, P=0.013). Breathing reserve was negatively correlated with SIIIN2, closing volume/vital capacity, and residual volume (RV) (r=-0.799, P<0.0001; r=-0.471, P=0.007; r=-0.401, P=0.025, respectively) and positively correlated with FEV1, forced vital capacity (FVC) and FEV1/FVC (r=0.721; P<0.0001; r=0.592, P=0.0004; r=0.670, P<0.0001, respectively). SIIIN2 and CAT were independently predictive of VO2 and breathing reserve at peak exercise. RV, FVC, and FEV1 were independently predictive of the SF36-physical component summary, SF36-mental component summary, and breathing reserve, respectively. The SGRQ did not present any independent variables that could explain the model. In stable COPD patients, inhomogeneity of ventilation explains a large degree of exercise intolerance assessed by CPETs and, to a lesser extent, poor quality of life.

Cardiopulmonary exercise testing and second-line pulmonary function tests to detect obstructive pattern in symptomatic smokers with borderline spirometry

BackgroundThe need for additional research on symptomatic smokers with normal spirometry has been recently emphasized. Albeit not meeting criteria for Chronic obstructive pulmonary disease (COPD) diagnosis, symptomatic smokers may experience activity limitation, evidence of airway disease, and exacerbations. We, therefore, evaluated whether symptomatic smokers with borderline spirometry (post-bronchodilator FEV1/FVC ratio between 5th to 20th percentile of predicted values) have pulmonary function abnormalities at rest and ventilatory constraints during exercise. Methods48 subjects (aged 60 ± 8 years, mean ± SD, 73% males, 16 healthy, and 17 symptomatic smokers) underwent cardiopulmonary exercise testing (CPET), body plethysmography, nitrogen single-breath washout test (N2SBW), lung diffusion for carbon monoxide (DLCO), and forced oscillation technique (FOT). ResultsCompared to healthy subjects, symptomatic smokers showed: 1) reduced breathing reserve (36 ± 17 vs. 49 ± 12%, P = 0.050); 2) exercise induced dynamic hyperinflation (−0.20 ± 0.17 vs. −0.03 ± 0.21 L, P = 0.043); 3) higher residual volume (158 ± 22 vs. 112 ± 22%, P < 0.001); 4) phase 3 slope at N2SBW (4.7 ± 2.1 vs. 1.4 ± 0.6%, P < 0.001); 5) no significant differences in DLCO and FOT results. ConclusionsIn smokers with borderline spirometry, CPET and second-line pulmonary function tests may detect obstructive pattern. These subjects should be referred for second line testing, to obtain a diagnosis, or at least to clarify the mechanisms underlying symptoms. Whether the natural history of these patients is similar to COPD, and they deserve a similar therapeutic approach is worth investigating.