scholarly journals Z-alpha1-antitrypsin polymers and small airways disease: a new paradigm in alfa-1 anti-trypsin deficiency-related COPD development?

2021 ◽  
Author(s):  
Laura Pini ◽  
Laura Tiberio ◽  
Marianna Arici ◽  
Luciano Corda ◽  
Jordan Giordani ◽  
...  
Keyword(s):  
Pulmonary Function Tests ◽  
Elisa Test ◽  
Inflammatory Activity ◽  
Phase Iii ◽  
Normal Lung ◽  
Closing Volume ◽  
Small Airways ◽  
Exhaled Breath ◽  
Alpha1 Antitrypsin ◽  
Never Smoker

The presence of Alpha1-Antitrypsin (AAT) polymers, known to promote a sustained pro-inflammatory activity, has been previously demonstrated in bronchial biopsies of subjects with Z-AAT deficiency (AATD) suggesting a possible role in the development of COPD through a small airway disease impairment. The study aimed to assess the presence of small airways dysfunction and the potential correlation with the presence of Z-AAT polymers obtained by Exhaled Breath Condensate (EBC) collection in PiZZ subjects, as compared with matched healthy PiMM subjects. We enrolled 19 asymptomatic, never smoker subjects: 9 PiZZ and 10 PiMM as controls, without obstructive ventilatory defect (i.e., normal FEV1/VC% ratio). All subjects underwent complete pulmonary function tests (PFT). EBC was collected in all subjects. ELISA test was applied to search for Z-AAT polymers. The PiZZ subjects showed normal lung volumes and DLCO values. However, in comparison with PiMM subjects, the single breath test N2 wash-out revealed significant differences regarding the phase III slope (1.45±0.35 N2/L vs. 0.96±0.40 N2/L) (p<0.02) in the PiZZ subjects, while the closing volume/vital capacity ratio (14.3±4.5 % vs. 11.3±6.3 %) was not significantly increased. The ELISA test detected the presence of Z-AAT polymers in 44% of PiZZ patients. Asymptomatic, never smoker PiZZ subjects with normal spirometry and lung diffusion capacity showed airways impairment when compared to PiMM subjects. Although Z-AAT polymers were found only in 44% of PiZZ subjects, these findings suggest the possibility that chronic bronchiolitis can develop as a result of the long-term pro-inflammatory activity of Z-AAT polymers in subjects with Z-related AATD.

Effect of an inhaled atropinelike agent on normal airway function

1979 ◽  
Vol 46 (2) ◽  
pp. 256-262 ◽  
Author(s):  
N. J. Douglas ◽  
M. F. Sudlow ◽  
D. C. Flenley
Keyword(s):  
Vagal Tone ◽  
Dynamic Compliance ◽  
Normal Subjects ◽  
Specific Conductance ◽  
Phase Iii ◽  
Closing Volume ◽  
Small Airways ◽  
Flow Rates ◽  
Peripheral Airways ◽  
Airway Function

Ten normal subjects inhaled 80 microgram ipratropium or placebo. Body plethysmograph studies showed that ipratropium increased specific conductance (0.14–0.21 s-1.cmH2O–1) and increased flow rates during both maximal and partial forced expiratory maneuvers at all volumes from 50 to 10% vital capacity (P less than 0.01). Ipratropium produced no change in quasi-static or dynamic compliance, closing volume, or the slope of phase III of the closing volume trace, but there was an increase in the height of phase IV (P less than 0.01). Specific conductance reflects central airways caliber, whereas flow rates at low lung volumes in the absence of alteration in static recoil pressure may reflect the caliber of more peripheral airways. We conclude that inhibition of vagal tone results in dilatation of large and small airways. Analysis of the flow volume results on the equal pressure point model suggests that the bronchodilatation normally resulting from the inhalation to total lung capacity is not solely due to inhibition of vagal tone.

scholarly journals Acute effects of long-acting bronchodilators on small airways detected in COPD patients by single-breath N2 test and lung P-V curve

2017 ◽  
Vol 123 (5) ◽  
pp. 1266-1275 ◽  
Author(s):  
Matteo Pecchiari ◽  
Pierachille Santus ◽  
Dejan Radovanovic ◽  
Edgardo DʼAngelo
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Phase Iii ◽  
Chronic Obstructive ◽  
Closing Volume ◽  
Small Airways ◽  
Acute Effects ◽  
Obstructive Pulmonary Disease ◽  
Single Breath ◽  
Volume Curve

Small airways represent the key factor of chronic obstructive pulmonary disease (COPD) pathophysiology. The effect of different classes of bronchodilators on small airways is still poorly understood and difficult to assess. Hence the acute effects of tiotropium (18 µg) and indacaterol (150 µg) on closing volume (CV) and ventilation inhomogeneity were investigated and compared in 51 stable patients (aged 70 ± 7 yr, mean ± SD; 82% men) with moderate to very severe COPD. Patients underwent body plethysmography, arterial blood gas analysis, tidal expiratory flow limitation (EFL), dyspnea assessment, and simultaneous recording of single-breath N2 test and transpulmonary pressure-volume curve (PL-V), before and 1 h after drug administration. The effects produced by indacaterol on each variable did not differ from those caused by tiotropium, independent of the severity of disease, assessed according to the Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) scale and the presence of EFL. Bronchodilators significantly decreased the slope of phase III and CV (−5 ± 4 and −2.5 ± 2.1%, respectively, both P < 0.001), with an increase in both slope and height of phase IV and of the anatomical dead space. Arterial oxygen pressure and saturation significantly improved (3 ± 3 mmHg and 2 ± 2%, respectively, both P < 0.001); their changes negatively correlated with those of phase III slope ( r = −0.659 and r = −0.454, respectively, both P < 0.01). The vital capacity (VC) increased substantially, but the PL-V/VC curve above CV was unaffected. In conclusion, bronchodilators reduce the heterogeneity of peripheral airway mechanical properties and the extent of their closure, with minor effects on critical closing pressure. This should lessen the risk of small-airway damage and positively affect gas exchange. NEW & NOTEWORTHY This is the first study investigating in stable chronic obstructive pulmonary disease patients the acute effects of two long-acting bronchodilators, a β-agonist and a muscarinic antagonist, on peripheral airways using simultaneous lung pressure-volume curve and single-breath N2 test. By lessening airway mechanical property heterogeneity, both drugs similarly reduced ventilation inhomogeneity and extent of small-airway closure, as indicated by the decrease of phase III slope, increased oxygen saturation, and fall of closing volume, often below expiratory reserve volume.

Small airway morphology and lung function in the transition from normality to chronic airway obstruction

2003 ◽  
Vol 95 (1) ◽  
pp. 441-447 ◽  
Author(s):  
Angelo Corsico ◽  
Manlio Milanese ◽  
Simonetta Baraldo ◽  
Gian Luca Casoni ◽  
Alberto Papi ◽  
...  
Keyword(s):  
Lung Function ◽  
Airway Obstruction ◽  
Pulmonary Function Tests ◽  
Lung Resection ◽  
Muscle Thickness ◽  
Forced Expiratory Volume ◽  
Normal Lung ◽  
Small Airways ◽  
Airway Wall ◽  
Normal Lung Function

This study investigated the relationships between pathological changes in small airways (<6 mm perimeter) and lung function in 22 nonasthmatic subjects (20 smokers) undergoing lung resection for peripheral lesions. Preoperative pulmonary function tests revealed airway obstruction [ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) < 70%] in 12 subjects and normal lung function in 10. When all subjects were considered together, total airway wall thickness was significantly correlated with FEV1/FVC ( r2 = 0.25), reactivity to methacholine ( r2 = 0.26), and slope of linear regression of FVC against FEV1 values recorded during the methacholine challenge ( r2 = 0.56). Loss of peribronchiolar alveolar attachments was significantly associated ( r2 = 0.25) with a bronchoconstrictor effect of deep inhalation, as assessed from a maximal-to-partial expiratory flow ratio <1, but not with airway responses to methacholine. No significant correlation was found between airway smooth muscle thickness and lung function measurements. In conclusion, this study suggests that thickening of the airway wall is a major mechanism for airway closure, whereas loss of airway-to-lung interdependence may contribute to the bronchoconstrictor effect of deep inhalation in the transition from normal lung function to airway obstruction in nonasthmatic smokers.

Fast vs. slow exhalation before O2 inhalation alters subsequent phase III slope

1984 ◽  
Vol 56 (1) ◽  
pp. 52-56 ◽  
Author(s):  
T. S. Hurst ◽  
B. L. Graham ◽  
D. J. Cotton
Keyword(s):  
Total Lung Capacity ◽  
Normal Subjects ◽  
Phase Iii ◽  
Breath Holding ◽  
Small Airways ◽  
Residual Volume ◽  
Lung Capacity ◽  
Single Breath ◽  
Subsequent Phase ◽  
Phase Iii Slope

We studied 10 symptom-free lifetime non-smokers and 17 smokers all with normal pulmonary function studies. All subjects performed single-breath N2 washout tests by either exhaling slowly (“slow maneuver”) from end inspiration (EI) to residual volume (RV) or exhaling maximally (“fast maneuver”) from EI to RV. After either maneuver, subjects then slowly inhaled 100% O2 to total lung capacity (TLC) and without breath holding, exhaled slowly back to RV. In the nonsmokers seated upright phase III slope of single-breath N2 test (delta N2/l) was lower (P less than 0.01) for the fast vs. the slow maneuver, but this difference disappeared when the subjects repeated the maneuvers in the supine position. In contrast, delta N2/l was higher for the fast vs. the slow maneuver (P less than 0.01) in smokers seated upright. For the slow maneuver, delta N2/l was similar between smokers and nonsmokers but for the fast maneuvers delta N2/l was higher in smokers than nonsmokers (P less than 0.01). We suggest that the fast exhalation to RV decreases delta N2/l in normal subjects by decreasing apex-to-base differences in regional ratio of RV to TLC (RV/TLC) but increases delta N2/l in smokers, because regional RV/TLC increases distal to sites of small airways obstruction when the expiratory flow rate is increased.

Emphysema

Chest Imaging ◽  
2019 ◽  
pp. 325-329
Author(s):  
Travis S. Henry ◽  
Brent P. Little
Keyword(s):  
Lung Disease ◽  
Pulmonary Function Tests ◽  
Disease Process ◽  
Normal Lung ◽  
Chronic Obstructive ◽  
Common Disease ◽  
Obstructive Pulmonary Disease ◽  
Cystic Lung ◽  
Emphysematous Lung ◽  
Different Parts

Emphysema is the abnormal, permanent enlargement of air spaces distal to the terminal bronchioles, accompanied by destruction of alveolar walls, but without obvious fibrosis. Chronic obstructive pulmonary disease (COPD) is a spectrum of obstructive lung diseases that includes emphysema and chronic bronchitis – diseases that frequently coexist, especially in smokers. Emphysema is an extremely common disease and in most cases the diagnosis is established with clinical data including pulmonary function tests (PFTs). CT may be helpful for clarifying the diagnosis in mild cases or if another disease process (such as interstitial lung disease) is suspected. The three different types of emphysema (centrilobular, paraseptal, and panlobular) affect different parts of the secondary pulmonary lobule and are easily distinguished on CT. Emphysema distorts the normal lung anatomy and can cause superimposed processes (e.g. pneumonia or pulmonary edema) to look atypical on chest radiography and CT. Similarly, lung cancer may have an unusual morphology when it arises within emphysematous lung. Cystic lung disease and honeycombing in pulmonary fibrosis should not be confused with emphysema. Cysts and honeycombing have defined walls on CT, whereas centrilobular emphysema manifests as areas of low attenuation without perceptible walls.

Aerosol penetrance: a sensitive index of peripheral airways obstruction

1976 ◽  
Vol 40 (3) ◽  
pp. 468-471 ◽  
Author(s):  
M. B. Dolovich ◽  
J. Sanchis ◽  
C. Rossman ◽  
M. T. Newhouse
Keyword(s):  
Chronic Obstructive Lung Disease ◽  
Outer Zone ◽  
Normal Subjects ◽  
Airway Disease ◽  
Chronic Obstructive ◽  
Closing Volume ◽  
Small Airways ◽  
Peripheral Airways ◽  
Sensitive Index ◽  
Airways Obstruction

Early injury of the small airways has been demonstrated in asymptomatic smokers. Ventilatory tests including the maximum midexpiratory flow rate and closing volume have been useful in clinical detection of small airways disease in symptomatic subjects. In the present study, airway “obstruction” was assessed aerodynamically by gamma camera measurements of chest radioactivity following the inhalation of 131I-labeled aerosol (aerodynamic mass median diameter 3 mum). Studies were performed in normal subjects, asymptomatic smokers, and patients with chronic obstructive lung disease. An aerosol penetrance index (AeP) was devised from determinations which involved 1) an analysis of central (inner zone) and peripheral (outer zone) deposition of aerosol in the lung and 2) a ratio of initial counts to 24-h counts in the periphery (outer zone) of the lung. AeP values were 41.5 +/- 11.5 for the normal group, 20.9 +/- 7.6 for the smoker group, and 10.6 +/- 5.2 for the subjects with chronic obstructive airway disease. AeP was significantly reduced in the smokers indicating that the AeP is a sensitive index of early peripheral airways obstruction.

scholarly journals Does the nitrogen single-breath washout test contribute to detecting pulmonary involvement in rheumatoid arthritis? A pilot study

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Elizabeth Jauhar Cardoso Bessa ◽  
Felipe de Miranda Carbonieri Ribeiro ◽  
Geraldo da Rocha Castelar Pinheiro ◽  
Agnaldo José Lopes
Keyword(s):  
Rheumatoid Arthritis ◽  
Pulmonary Function Tests ◽  
Airway Disease ◽  
Pulmonary Involvement ◽  
Phase Iii ◽  
Ventilation Distribution ◽  
Lung Capacity ◽  
Single Breath ◽  
Small Airway Disease ◽  
Phase Iii Slope

Abstract Objective There has been growing interest in studying small airway disease through measures of ventilation distribution, thanks to the resurgence of the nitrogen single-breath washout (N2SBW) test. Therefore, this study evaluated the contribution of the N2SBW test to the detection of pulmonary involvement in patients with rheumatoid arthritis (RA). Results Twenty-one patients with RA underwent clinical evaluation, pulmonary function tests (PFTs), including the N2SBW test, and computed tomography (CT). The main tomographic findings were air trapping and bronchiectasis (57.1% and 23.8% of cases, respectively). According to the phase III slope of the N2SBW (phase III slope), 11 and 10 patients had values < 120% predicted and > 120% predicted, respectively. Five patients with limited involvement on CT had a phase III slope > 120%. The residual volume/total lung capacity ratio was significantly different between patients with phase III slopes < 120% and > 120% (P = 0.024). Additionally, rheumatoid factor positivity was higher in patients with a phase III slope > 120% (P = 0.021). In patients with RA and airway disease on CT, the N2SBW test detects inhomogeneity in the ventilation distribution in approximately half of the cases, even in those with normal conventional PFT results.

Gravitational independence of single-breath washout tests in recumbent dogs

1988 ◽  
Vol 64 (2) ◽  
pp. 642-648 ◽  
Author(s):  
S. Tomioka ◽  
S. Kubo ◽  
H. J. Guy ◽  
G. K. Prisk
Keyword(s):  
Prone Position ◽  
Regional Distribution ◽  
Transpulmonary Pressure ◽  
Phase Iii ◽  
Closing Volume ◽  
Body Rotation ◽  
Single Breath ◽  
Volume Curve ◽  
Pressure Volume Curve ◽  
Phase Iv

To examine the mechanisms of lung filling and emptying, Ar-bolus and N2 single-breath washout tests were conducted in 10 anesthetized dogs (prone and supine) and in three of those dogs with body rotation. Transpulmonary pressure was measured simultaneously, allowing identification of the lung volume above residual volume at which there was an inflection point in the pressure-volume curve (VIP). Although phase IV for Ar was upward, phase IV for N2 was small and variable, especially in the prone position. No significant prone to supine differences in closing capacity for Ar were seen, indicating that airway closure was generated at the same lung volumes. The maximum deflections of phase IV for Ar and N2 from extrapolated phase III slopes were smaller in the prone position, suggesting more uniform tracer gas concentrations across the lungs. VIP was smaller than the closing volume for Ar, which is consistent with the effects of well-developed collateral ventilation in dogs. Body rotation tests in three dogs did not generally cause an inversion of phase III or IV. We conclude that in recumbent dogs regional distribution of ventilation is not primarily determined by the effect of gravity, but by lung, thorax, and mediastinum interactions and/or differences in regional mechanical properties of the lungs.

Regional deposition of 3.6-micron particles and lung function in asthmatic subjects

1991 ◽  
Vol 71 (6) ◽  
pp. 2238-2243 ◽  
Author(s):  
M. Svartengren ◽  
M. Anderson ◽  
G. Bylin ◽  
K. Philipson ◽  
P. Camner
Keyword(s):  
Airway Resistance ◽  
Regression Line ◽  
Test Phase ◽  
Phase Iii ◽  
Poor Correlation ◽  
Small Airways ◽  
Single Breath ◽  
Regional Deposition ◽  
Severe Asthmatic ◽  
Highly Correlated

In a group of moderately severe asthmatic subjects, regional deposition of 3.6-microns (aerodynamic diameter) monodispersed Teflon particles labeled with 111In was studied twice. The particles were inhaled with maximally deep inhalation at 0.5 l/s. Lung retention was measured at 0, 6, 24, and 48 h by use of a profile scanner equipped with two 13 x 5-cm NaI crystals. The retentions at 24 (Ret24) and 48 h were highly correlated (r = 0.96 with a slope of the regression line close to 1). There was a poor correlation between retention at 6 h and Ret24 (r = 0.54). The Ret24 values at the two exposures were well correlated (r = 0.86). There were significant correlations between airway resistance as well as single-breath nitrogen test phase III and Ret24 (r = 0.70 and 0.67, respectively). The correlation between single-breath nitrogen test phase III and Ret24 persisted also when only subjects within a narrow interval of airway resistance were included. The study indicates that regional deposition can be studied by measurements of Ret24 in subjects with moderately severe asthma and that it is dependent on changes in both large and small airways.

A two-compartment model of pulmonary nitric oxide exchange dynamics

1998 ◽  
Vol 85 (2) ◽  
pp. 653-666 ◽  
Author(s):  
Nikolaos M. Tsoukias ◽  
Steven C. George
Keyword(s):  
Nitric Oxide ◽  
Elimination Rate ◽  
Compartment Model ◽  
Phase Iii ◽  
Exhaled Breath ◽  
Dynamic Relationship ◽  
Exhaled No ◽  
Two Compartment Model ◽  
Conducting Airways ◽  
The Relationship

The relatively recent detection of nitric oxide (NO) in the exhaled breath has prompted a great deal of experimentation in an effort to understand the pulmonary exchange dynamics. There has been very little progress in theoretical studies to assist in the interpretation of the experimental results. We have developed a two-compartment model of the lungs in an effort to explain several fundamental experimental observations. The model consists of a nonexpansile compartment representing the conducting airways and an expansile compartment representing the alveolar region of the lungs. Each compartment is surrounded by a layer of tissue that is capable of producing and consuming NO. Beyond the tissue barrier in each compartment is a layer of blood representing the bronchial circulation or the pulmonary circulation, which are both considered an infinite sink for NO. All parameters were estimated from data in the literature, including the production rates of NO in the tissue layers, which were estimated from experimental plots of the elimination rate of NO at end exhalation (ENO) vs. the exhalation flow rate (V˙E). The model is able to simulate the shape of the NO exhalation profile and to successfully simulate the following experimental features of endogenous NO exchange: 1) an inverse relationship between exhaled NO concentration and V˙E, 2) the dynamic relationship between the phase III slope andV˙E, and 3) the positive relationship between ENO andV˙E. The model predicts that these relationships can be explained by significant contributions of NO in the exhaled breath from the nonexpansile airways and the expansile alveoli. In addition, the model predicts that the relationship between ENO and V˙E can be used as an index of the relative contributions of the airways and the alveoli to exhaled NO.

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