Single-breath Nitrogen Research Articles

Usefulness of Colored 3D Imaging of Respiratory Impedance in Asthma

PurposeRecently, the clinical application of the forced oscillation technique (FOT) has progressed with the spread of commercially available FOT devices, including the impulse oscillation system and MostGraph. We investigated the usefulness of color 3D imaging of respiratory impedance in asthma using MostGraph.MethodsWhole-breath and within-breath respiratory system resistance (Rrs) and reactance (Xrs) were measured in 78 patients with asthma. Color 3D images were classified into three patterns: the chronic obstructive pulmonary disease (COPD)-like pattern (high values of Rrs and Xrs with a marked respiratory cycle and frequency dependence), the asthma pattern (moderately high Rrs over the entire frequency and a respiratory cycle with slight Xrs changes), and a normal-like pattern (low Rrs and Xrs with few within-breath changes). The classification was performed by three researchers, who were unaware of the clinical information, and the clinical characteristics were compared among the three groups.ResultsColor 3D imaging provided a COPD-like pattern in 25 patients, an asthma pattern in 39 patients, and a normal-like pattern in 14 patients. Patients with the COPD-like pattern were predominantly female with a higher body mass index, lower forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), and higher Rrs and Xrs values (whole-breath and within-breath variation). Those with the normal pattern had higher FEV1 and FVC, and a lower single-breath nitrogen washout slope. There were no differences in asthma control or exhaled nitric oxide levels among the three groups.ConclusionsThese results suggest that color 3D imaging of respiratory impedance may show asthma phenotypes.

Assessing and accessing the small airways; implications for asthma management

Despite the wealth of experience in the management of asthma, the disease remains inadequately controlled in some patients, who face long-term respiratory impairment and disability. The disease has been characterised as an inflammatory condition affecting first the larger airways and eventually the smaller airways, but there is evidence that peripheral airway involvement defines a particular and more severe phenotype of asthma. For this reason, assessing functional and biological parameters reflective of small airways involvement is important prognostically. No assessment method is universally and directly representative of peripheral airway function, but the traditional spirometric tests, including vital capacity, residual volume and forced vital capacity, are somewhat correlated with this function; useful methods for further assessment include the single-breath nitrogen wash-out test, impulse oscillometry, nitrous oxide and exhaled breath concentrate measurements, as well as computed tomography to reflect air trapping and response to treatment. Formulation advancements have made for easier treatment access to the smaller airways, with the new extrafine formulations resulting in better asthma control compared with non-extrafine formulations.

The Relationship Between Airflow Obstruction, Emphysema Extent, and Small Airways Function in COPD

The severities of COPD (FEV(1) % predicted) and airflow obstruction (FEV(1)/FVC) are considered to be due to both emphysema and small airways disease. To our knowledge, this has not been previously confirmed by combined measurements of emphysema and of small airway function. We hypothesized that small airways disease and emphysema extent contribute independently to the severity of both COPD and airflow obstruction. Twenty-six subjects with COPD underwent measurements with forced oscillation technique (FOT) at 6 Hz and single-breath nitrogen washout. Respiratory system resistance, respiratory system reactance (Xrs), and expiratory flow limitation (EFL) index (measured as mean inspiratory Xrs − expiratory Xrs) were derived from FOT. Closing volume/vital capacity (CV/VC) was derived from the washout. Emphysema extent was measured as low attenuation areas < -910 Hounsfield units, expressed as a percentage of CT scan lung volume from multislice CT scans taken at total lung capacity. Subjects were aged (mean ± SD) 69.6 ± 8.0 years. Postbronchodilator FEV(1) was 64.8 ± 19.8% predicted, and diffusing capacity of lung for carbon monoxide was 50.7 ± 15.8% predicted. Emphysema extent was 22.6% ± 15.0% CT scan volume. CV/VC was 16.9% ± 7.9%; Xrs, -3.72 ± 3.03 cm H(2)O/L/s; and EFL index, 3.88 ± 3.93 cm H(2)O/L/s. In multiple regression analyses, FEV(1)/FVC was predicted by both emphysema and CV/VC (model r(2) = 0.54, P < .0001) whereas FEV(1) % predicted was predicted by emphysema and EFL index (model r(2) = 0.38, P = .0014). The severities of COPD and airflow obstruction are independently predicted by both small airways disease and emphysema extent.

Drobne drogi oddechowe w chorobach obturacyjnych płuc

The term small airways (SA) applies to the bronchi below 7th generation with diameter smaller than 2 mm. This paper presents data showing that this part of the respiratory system is distinct in terms of its architecture, physiology and pathophysiology. The most important role SA play in obstructive airway diseases. In healthy subjects SA resistance accounts for 10% of the total airway resistance while in patients with obstructive disease, due to the constriction of the airways together with airway inflammation, SA are responsible even for 60% of the total resistance. Changes in SA in asthma and COPD are responsible for air trapping especially prominent in the latter disease. There are no precise tools to diagnose SA. Depending availability and experience HRCT, body pletysmography (RV/TLS plus other parameters) are frequently used. Some hope for the future is placed in combined use of oscilometry, multiple (or single) breath nitrogen wash-out and eNO concentration measurement. Due to our increasing knowledge on the role of SA in airway obstruction ultra-fine particle aerosols have been developed that penetrate to this compartment of the respiratory system (deposition confirmed in cascade impactors as well as by ozone scans after aerosol inhalation). Authors present selected publications investigating whereas deep drug penetration influences its clinical efficacy. For LABAs deposition in SA doesn't seem to increase their bronchodilating effect. Using ultrafine CS aerosol allows to maintain clinical effects even with half the dose of the active steroid, however. In summary, SA seem to be crucial in obstructive diseases of the airways and therefore constitute an important target for therapy.

Respiratory symptoms and peripheral airways disease in a cross-sectional study on a random population sample

ObjectivesRespiratory symptoms are associated with spirometry results but more strongly with smoking history, suggesting that alterations in the lung other than those revealed by spirometry contribute to cause symptoms. Smoking...

Prediction of BOS by the single-breath nitrogen test in double lung transplant recipients

BackgroundThe present study analyses the ability of the alveolar slope of the single-breath nitrogen washout test (N2-slope) to diagnose and predict the development of the bronchiolitis obliterans syndrome (BOS).MethodsWe present a retrospective analysis of 61 consecutive bilateral lung or heart-lung transplant recipients who were followed at regular control visits during a three year follow-up. The operating characteristics of the N2-slope to diagnose BOS and potential BOS (BOS 0-p) and to predict BOS were determined based on cut off values of 95% specificity.ResultsThe sensitivity of the N2-slope to identify BOS was 96%, and BOS 0-p 100%. The predictive ability to predict BOS with a N2-slope > 478% of the predicted normal was 56%, and if combined with a coincident FEV1 < 90% of the basal value, the predictive ability was 75%.ConclusionsThe predictive ability of either the N2-slope or of FEV1 to diagnose BOS is limited but the combination of the two appears useful. Follow-up protocols of bilateral lung and heart-lung transplant recipients should consider including tests sensitive to obstruction of the peripheral airways.

Pathophysiology of Evolution of Small Airways Disease to Overt COPD

ABSTRACTBackground: The slope of phase III (single breath nitrogen test), an index of ventilation inhomogeneity, has been used for early detection of COPD. Tidal airway closure (cyclic opening and closure of the peripheral airways during tidal breathing; ACT) and expiratory flow limitation (attainment of maximal expiratory flow during tidal expiration; EFLT) cause small airways disease (SAD). The relationships of these indices with COPD severity may reflect the progress from SAD to overt COPD. Methods: In this cross-sectional study we have assessed for the first time the phase III slope, ACT and EFLT in 10 smokers with normal spirometry (group O) and 40 COPD patients with GOLD scores from I to IV. Results: In most group O smokers the phase III slope was increased, and further increased with GOLD severity (up to 800%pred in GOLD IV). A close correlation was found of slope with GOLD (r = 0.77). ACT was absent in smokers with normal spirometry and in most patients with mild COPD. EFLT first appeared in GOLD II patients and its prevalence progressively increased in GOLD III and IV patients. Conclusions: Most group O smokers exhibit increased phase III. With overt COPD there is a progressive increase in phase III and reduction of FEV1/FVC ratio from GOLD I to IV. A reduction of FEV1 occurs from GOLD stage II. As the disease progresses from moderate to severe, there is an increasing presence of ACT. Tidal EFL, with dynamic hyperinflation and severe dyspnea is present only in GOLD III and IV.

Effects of extra‐fine inhaled beclomethasone/formoterol on both large and small airways in asthma

Airway inflammation in asthma involves both large and small airways, and the combination of inhaled corticosteroids (ICS) and long acting beta-2 agonists (LABA) is the mainstay of therapy. Available inhaled combinations differ in terms of drug delivery to the lung and the ability to reach small airways. To evaluate whether treatment with an extra-fine inhaled combination provides additional effects vs a nonextra-fine combination on airway function. After a 1- to 4-week run-in period, patients with asthma were randomized to a double blind, double dummy, 12-week treatment with either extra-fine beclomethasone/formoterol (BDP/F) 400/24 microg daily or fluticasone propionate/salmeterol (FP/S) 500/100 microg daily. Methacholine (Mch) bronchoprovocation challenge and single breath nitrogen (sbN2) test were performed. Thirty patients with asthma (15 men), mean age 43, mean forced expiratory volume in the first second (FEV(1)) 71.4% of predicted, were included. A significant increase (P < 0.01) versus baseline was observed in predose FEV(1) in both BDP/F and FP/S groups (0.37 +/- 0.13 l and 0.36 +/- 0.12 l, respectively). PD(20)FEV(1) Mch improved significantly from 90.42 (+/-30.08) microg to 432.41 (+/-122.71) microg in the BDP/F group (P = 0.01) but not in the FP/S group. A trend toward improvement vs baseline was observed for BDP/F in closing capacity (CC), whereas no differences were recorded in other sbN(2) test parameters. The findings of this pilot study suggest that an extra-fine inhaled combination for the treatment of asthma has beneficial effects on both large and small airways function as expressed by Mch and sbN(2) tests.

Effect of the inhaled corticosteroid mometasone on small airway patency in patients with asthma

The inflammation in asthma involves both the large and the small airways. This study was designed to examine whether mometasone delivered from a dry powder inhaler would improve those parameters thought to reflect patency and obstruction of the small airways (diameter <2 mm). Subjects with mild to moderate asthma, only receiving short-acting beta-agonists, underwent baseline assessment, and then were randomized to receive for 12 weeks either mometasone 400 micrograms once daily in the evening or matching placebo. Outcomes assessed included clinical measures and measures of airway responsiveness and inflammation included methacholine sensitivity (concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second [FEV(1)] [PC(20)]), exhaled nitric oxide, serum ECP, and sputum eosinophils. Pulmonary function was assessed by spirometry, plethysmography, and forced oscillometry. Measures of small airway patency included single breath nitrogen washout and air trapping on expiratory high-resolution computed tomography. Results were available on 12 adult subjects who received mometasone and 14 subjects who received placebo. Among tests reflecting small airway patency, the forced expiratory flow between 25 and 75% of vital capacity was significantly improved by mometasone compared with placebo (+9% versus -6%; p = 0.006 and the closing volume over forced vital capacity (FVC; -2% versus 0%; p = 0.05). Other results significantly favoring mometasone over placebo included FEV(1), FVC, PC(20), and A.M. and P.M. peak expiratory flows, and albuterol use. Mometasone delivered by a dry powder inhaler improved asthma control and pulmonary function in tests reflecting both large and small airways.

How to interpret reduced forced expiratory volume in 1 s (FEV1)/vital capacity ratio with normal FEV1

The aim of the present study was to determine whether the combination of low forced expiratory volume in 1 s (FEV(1))/vital capacity (VC) ratio with normal FEV(1) represents a physiological variant or a sign of early airflow obstruction. We studied 40 subjects presenting with low FEV(1)/VC, but FEV(1) within the range of normality predicted by European Respiratory Society reference equations, and 10 healthy controls. All subjects completed two questionnaires and underwent comprehensive pulmonary function testing, which included methacholine challenge and single-breath nitrogen wash-out. According to the questionnaires, the subjects were assigned to three groups, i.e. rhinitis (n = 8), bronchial asthma (n = 13) and chronic obstructive pulmonary disease (COPD; n = 12). Subjects with negative responses to questionnaires were assigned to an asymptomatic group (n = 7). Airway hyperresponsiveness was found in four subjects of the rhinitis group, all of the asthma group, and 10 of the COPD group; in the last two groups, it was associated with signs of increased airway closure and gas trapping. Bronchodilator response to salbutamol was positive in only a few individuals across groups. In the asymptomatic group, no significant functional changes were observed, possibly suggesting dysanaptic lung growth. In subjects with low FEV(1)/VC and normal FEV(1), questionnaires on respiratory symptoms together with additional pulmonary function tests may help to clarify the nature of this pattern of lung function.

Ciclesonide improves measures of small airway involvement in asthma

Ciclesonide is delivered as a small-particle inhaled corticosteroid and improves lung function and airway hyperresponsiveness. The objective of the present study was to assess whether ciclesonide can specifically improve small airway function in asthma. A total of 16 mild-to-moderate asthma patients (seven males; median (range) age 39 (19-56) yrs and forced expiratory volume in one second (FEV(1)) 89 (62-120)% predicted) were randomised to 5 weeks' treatment with placebo or 320 mug ciclesonide once daily. The following small airway parameters were assessed: mean forced expiratory flow between 25 and 75% of forced vital capacity (FVC), percentage fall in FVC at provocative dose of adenosine-5'-monophosphate and of methacholine (MCh) causing a 20% fall in FEV(1), expiratory lung volume on computed tomography (CT) scan after MCh challenge, single-breath nitrogen closing volume and alveolar exhaled nitric oxide (eNO). Seven subjects received placebo and nine received ciclesonide. Both alveolar eNO and CT measurements of expiratory lung volume after MCh challenge decreased significantly with ciclesonide (median (range) decrease 4.4 (54.8-1.4) ppb and 59 (1,569- -117) mL, respectively), and compared with placebo (-0.4 (7.3- -3.4) ppb and -121 (20- -236) mL respectively). Ciclesonide did not significantly improve other small airways parameters. Inflammation and patency of small airways, reflected by alveolar exhaled nitric oxide and air trapping on computed tomography scan, both improve with ciclesonide even in this small number of patients. This indicates that ciclesonide exerts anti-inflammatory effects on small airways.

A 4-Dimensional Model of the Alveolar Structure

The alveolar structure, a space-filling branching duct system with alveolar openings, is one of the most complicated structures in the living body. Although its deformation during ventilation is the basic knowledge for lung physiology, there has been no consensus on it because of technical difficulties of dynamic 3-dimensional observation in vivo. It is known that the alveolar duct wall (primary septa) in the fetal lung is deformed so as to obtain the largest inner space and the widest surface area, and that the secondary septa grow just before birth and their free ridges form the alveolar entrance rings (mouths) containing abundant elastin fibers. We have constructed a 4-dimensional alveolar model according to this morphogenetic process, where the alveolar deformation is modeled by a combination of springs and hinges, corresponding to elastin fibers at alveolar mouths and junctions of alveolar septa, respectively. The model includes a hypothesis that alveolar mouths are closed at minimum volume and that closed alveoli are stabilized by the alveolar lining liquid film containing a surfactant. Morphometric characteristics of the model were consistent with previous reports. Furthermore, the model explained how the alveolar number and size could change during ventilation. Using in vivo microscopy, we validated our model by an analysis of the dynamic inflation and deflation of subpleural alveoli. Our model, including the alveolar mouth-closure hypothesis, can explain the origin of phase IV in a single breath nitrogen washout curve (closing volume) and mechanism of alveolar recruitment/derecruitment.

A Novel Interpretation of Closing Volume Based on Single-Breath Nitrogen Washout Curve Simulation

Although closing volume is regarded as a clinical test for the early detection of peripheral airway closure, its grounds are not clear. There have been no simulation studies for phase IV in the single-breath nitrogen washout (SBNW) curve, even though several mathematical models for phase III have been proposed. We modeled the lung tissue deformation during slow expiration in which the tissue was regarded as a porous elastic body similar to a sponge. We assigned the maximum tissue density of lung parenchyma over which the lung tissue could not be contracted according to several experimental reports in literature. SBNW curves were then simulated by computing expired air volume and nitrogen concentration for respective acini in the lung model. The simulated SBNW curves well reproduced phase IV, cardiac oscillation, and its postural changes. We found that the higher lung compliance increased closing volume, but decreased residual volume. The smaller maximum tissue density generated larger closing volume and larger residual volume. It suggested that phase IV reflected the alveolar contractility, and the increase of closing volume in emphysema could be explained by an insufficient contraction of alveoli. We also found that the distribution of maximum tissue density affected the onset of Phase IV. A constant value of density generated a clear onset, but a wide distribution of it corresponding to peripheral airway closure obscured it. We suggest that the airway closure was not necessary for phase IV appearance in both normal and emphysematous lung.

Ventilation inhomogeneity in 1-antitrypsin-deficient emphysema

The slope of phase III of the single-breath nitrogen wash-out test (sbN2-test) measures ventilation inhomogeneity and, in smokers, is strongly associated with small airways pathology. The present authors aimed to study ventilation inhomogeneity in emphysema related to type Z alpha1-antitrypsin (AAT) and to assess its relationship with indices of parenchymal damage and airways obstruction. A total of 18 subjects, consisting of ex-smokers with type Z AAT and emphysema (confirmed by computed tomography scan), were studied in a cross-sectional design. Post-bronchodilation flow-volume curves and gas transfer parameters were measured; sbN2-test curves were obtained and the slope of phase III was determined. The mean value of the slope (4.6+/-1.3% N2 x L(-1)) was higher than reference values +2sd; it was significantly correlated with the transfer factor of the lung for carbon monoxide (R = -0.75) and the transfer coefficient of the lung for carbon monoxide (R = -0.58), but not with airways obstruction. There was no correlation between phase III slope values and cumulative smoking. In patients with type Z alpha1-antitrypsin emphysema, the increased ventilation inhomogeneity predominantly reflects parenchymal abnormalities, demonstrating that measurement of airways obstruction is not sufficient to characterise the disease. Determination of the sensitivity of the single-breath nitrogen wash-out test slope in detecting disease progression may give complementary information to spirometry.

Alveolar nitric oxideversusmeasures of peripheral airway dysfunction in severe asthma

Alveolar nitric oxide (NO) is a measure of peripheral airway inflammation in asthma, potentially associated with disease severity. The relationship between alveolar NO and physiological tests of peripheral airway (dys)function has not been investigated. The present authors hypothesised that peripheral airway inflammation and dysfunction are inter-related and associated with asthma severity. Alveolar NO was compared between 17 patients with mild-to-moderate asthma and 14 patients with severe asthma and related to total lung capacity (TLC), residual volume (RV)/TLC, thoracic gas volume (FRC), slope of the single breath nitrogen washout curve (dN2), closing capacity (CC)/TLC and fall in forced vital capacity at the provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second. In patients with severe asthma, strong correlations were found between alveolar NO and RV/TLC % pred, FRC % pred, dN2, and CC/TLC. Patients with oral steroid-dependent asthma had higher alveolar NO levels (2.7 ppb) compared with the other patients with severe (0.6 ppb) and mild-to-moderate asthma (0.3 ppb). The present authors conclude that alveolar nitric oxide is closely related to parameters of peripheral airway dysfunction in patients with severe asthma, and that oral steroid-dependent asthmatics have more peripheral airway disease than nonsteroid-dependent asthmatics. This suggests that patients on chronic oral steroid treatment have more extensive disease and require additional anti-inflammatory treatment to better target the peripheral airways.

Nitrogen washout slope in poorly controlled asthma

Short-term control of asthma is often lacking even though forced expiratory volume in 1 s (FEV1) remains above normal value. Small airways are a potential key site of persistent inflammation and structural modification. Noninvasive assessment of small airways was found to be difficult, but the computerized single breath nitrogen washout test (SBNT) has been recently successfully reintroduced with this aim. Twenty-four asthmatics (13 females) of various severity but with normal FEV1 were compared with 24 healthy volunteers (13 females) and studied at steady-state after bronchodilatation (400 microg salbutamol). Spirometric values, plethysmographic data, phase III (slope of phase III of the SBNT, dN2) and IV [closing volume (CV), with closing capacity (CC) = CV + residual volume (RV)] of the SBNT were checked. Asthma severity, recent control, exacerbation rate, and therapy requirements were assessed on the basis of validated questionnaires (ACQ) and international guidelines. Patients were prospectively pooled into two equal groups according to their exacerbation rate. The reproducibility of the measurements obtained on 2 following days was assessed. All plethysmographic values, except total lung capacity (TLC), differentiated asthmatic patients from controls. The CC/TLC [124 (117-148) vs 117 (112-123), P = 0.04] and dN2 [110 (99-190) vs 94 (75-111), P = 0.02] were increased in asthma. The dN2 was significantly increased in patients with frequent exacerbations [100 (83-105) vs 195 (141-212), P = 0.0005]. A correlation was obtained between dN2 and recent asthma control (rho: 0.62; P = 0.003), number of exacerbations (rho: 0.71, P = 0.0008), and RV/TLC (rho: 0.49, P = 0.026). This study demonstrated that ventilation inequalities assessed by dN2 represent an important indicator of poor asthma control and high exacerbation rate in high symptom perceivers. New therapies focused on small airways should now be developed.

Hydrofluoroalkane-134A Beclomethasone or Chlorofluorocarbon Fluticasone: Effect on Small Airways in Poorly Controlled Asthma

Inflammation in asthma extends into the small airways (< 2 mm diameter). Most inhaled corticosteroids are suspensions with a particle size > 2 mm. Therefore, inflammation in the small airways of patients with asthma may not be adequately treated with these preparations. Some inhaled corticosteroids, on the other hand, are compounded with alcohol, resulting in a solution producing an aerosol that has a mean particle diameter of < 2 mm. This study was designed to compare the addition of equivalent amounts of two inhaled corticosteroids (one a suspension and one a solution) to the treatment of patients with asthma, which was uncontrolled despite treatment with moderate to high doses of inhaled corticosteroids and usually additional controller medications. The study was performed with 30 patients, ≥ 18 years of age. Subjects were randomized in a single-blind fashion to receive, in addition to their current asthma therapy, either CFC-FP 220 µg each morning and 110 µg each evening (n = 10) or HFA-BDP 160 mcg twice daily (n = 20). Pre- and postbronchodilator spirometry, single breath nitrogen washout for closing volume and residual volume by plethysmography were assessed before and after 3 months of therapy. In the subjects who received HFA-BDP, the ratio of closing volume (CV) to vital capacity (VC) and residual volume (RV) decreased significantly (p = 0.0214 and 0.0433, respectively), whereas forced expiratory flow over 25–75% of the vital capacity (FEF25–75%), forced expiratory volume in 1 second (FEV1), and morning peak flow improved significantly (p = 0.0014, 0.0184, and 0.0321). Improvements from baseline of CV, CV/VC, and postbronchodilator FEF25–75%, were statistically significant in the HFA-BDP group compared with the CFC-FP group (p = 0.0049, 0.0194, and 0.0355, respectively). These preliminary findings suggest that the addition of HFA-BDP, compared with CFC-FP in patients with poorly controlled asthma despite receiving moderate to high doses of inhaled steroids, has a greater effect on parameters reflecting small airway patency presumably secondary to reduction in inflammation.

A comparison of two methods for measuring airway distensibility: nitrogen washout and the forced oscillation technique

The measurement of airway stiffness is an important tool for studying airway remodelling in asthma. The relationship between airway calibre and lung volume (airway distensibility) was measured by forced oscillation technique (FOT) and compared with that measured by single-breath nitrogen washout (SBNW). In four non-asthmatic healthy subjects and three asthmatics, anatomical dead space (VDF) was measured by SBNW and respiratory system conductance (Grs) was measured by FOT at 6 Hz. During SBNW testing, 0.5 l oxygen boluses were inhaled from three different lung volumes: functional residual capacity (FRC), 1 l above FRC and near total lung capacity (TLC). Following inhalation of the oxygen bolus subjects exhaled to residual volume and then inhaled to TLC. During FOT, subjects breathed 0.5–1.0 l tidal volumes but with gradually increasing end-expiratory lung volume until close to TLC, then returned to normal breathing before inhaling to TLC. This was also repeated but with reducing lung volume from TLC. Absolute lung volumes were measured by body plethysmography and related to volumes during FOT and SBNW by reference to TLC obtained at the end of each SBNW or FOT test manoeuvre. Distensibility was calculated as the linear regression slopes of VDF or Grs versus lung volume. Distensibility measured by VDF ranged 16–37 ml l−1 lung volume and by Grs it ranged 0.06–0.19 l s−1 cmH2O−1 l−1 lung volume. Both distensibility measurements were correlated (Pearson's R2 = 0.91, p = 0.001). The SBNW and FOT are comparable methods for measuring airway distensibility and may have similar clinical usefulness. However, further studies are required to make any specific inferences about the relationship between airway distensibility by FOT and airway remodelling.

Computerized single-breath nitrogen washout: predicted values in a rural French community.

Comparative manual and computer measurements of the alveolar N2 slope and closing volumes have indicated systematic differences. When a computerized system is used in field surveys, predicted values are to be obtained under the same conditions. Therefore, we measured the alveolar nitrogen slope (phase III, PIII), closing volume (CV), and closing capacity (CC) from single-breath N2 washout maneuvers in 158 healthy subjects (68 females), ages 21 to 64 years, from a rural community living in a nonpolluted area of northeast France. PIII, the CV to vital capacity ratio (CV:VC, %), and the CC to the total lung capacity ratio (CC:TLC, %) were regressed against age, height, weight, and the body mass index (BMI, kg/m2) and prediction equations with 95% confidence intervals were computed. PIII increased with age in both sexes and tended to decrease with height in males (r = -0.19, p = .08). The CV:VC and CC:TLC ratios depended on age and, in males, increased with the BMI. Despite accepting a 15% difference between the test VC and the spirometric VC, only 46.3% of asymptomatic nonsmokers produced a valid single-breath nitrogen washout (SBN2) test. This high failure rate limits the usefulness of the test for epidemiologic purposes when older populations "naive" to pulmonary function testing are studied under field-survey conditions.

Hydrofluoroalkane-134a beclomethasone or chlorofluorocarbon fluticasone: Effect on small airways in poorly controlled asthma

Inflammation in asthma extends into the small airways ( 2 mm. Therefore, inflammation in the small airways of patients with asthma may not be adequately treated with these preparations. Some inhaled corticosteroids, on the other hand, are compounded with alcohol, resulting in a solution producing an aerosol that has a mean particle diameter of < 2 mm. This study was designed to compare the addition of equivalent amounts of two inhaled corticosteroids (one a suspension and one a solution) to the treatment of patients with asthma, which was uncontrolled despite treatment with moderate to high doses of inhaled corticosteroids and usually additional controller medications. The study was performed with 30 patients, � 18 years of age. Subjects were randomized in a single-blind fashion to receive, in addition to their current asthma therapy, either CFC-FP 220 mg each morning and 110 mg each evening (n = 10) or HFA-BDP 160 mcg twice daily (n = 20). Pre- and postbronchodilator spirometry, single breath nitrogen washout for closing volume and residual volume by plethysmography were assessed before and after 3 months of therapy. In the subjects who received HFA-BDP, the ratio of closing volume (CV) to vital capacity (VC) and residual volume (RV) decreased significantly ( p = 0.0214 and 0.0433, respectively), whereas forced expiratory flow over 25 – 75% of the vital capacity (FEF25 – 75%), forced expiratory volume in 1 second (FEV1), and morning peak flow improved significantly ( p = 0.0014, 0.0184, and 0.0321). Improvements from baseline of CV, CV/VC, and postbronchodilator FEF25 – 75%, were statistically significant in the HFA-BDP group compared with the CFC-FP group ( p = 0.0049, 0.0194, and 0.0355, respectively). These preliminary findings suggest that the addition of HFA-BDP, compared with CFC-FP in patients with poorly controlled asthma despite receiving moderate to high doses of inhaled steroids, has a greater effect on parameters reflecting small airway patency presumably secondary to reduction in inflammation.