Single-breath Nitrogen Washout Research Articles

CHRONIC OBSTRUCTION OF PERIPHERAL AIRWAYS AND HYPOXEMIA IN ASTHMATIC CHILDREN

Both in vivo and in excised lungs, the nitrogen washout alveolar plateau (phase 3 slope) correlates with histopathologically detected obstruction of peripheral airways. We hypothesized that children with abnormally steep phase 3 slopes between episodes of asthma should exhibit both hypoxemia and relatively severe clinical courses because of chronic obstruction of peripheral airways. To test this, we measured phase 3 slope and supine arterial oxygen saturation (SaO2, by ear oximetry) and reviewed the clinical histories of 25 children in stable condition between episodes of wheezing. We found that the 7 children with abnormally steep phase 3 slopes also had the lowest values for SaO2 (mean 93.7±1.4 SD %). Phase 3 slope had a significant negative correlation with SaO2. There was no correlation between SaO2 and expiratory flow rate, density dependence of expiratory flow or the ratio of residual volume to total lung capacity. During the year preceding the study, outpatient visits resulting in injections of adrenaline were significantly more frequent in the 7 children with steep phase 3 slopes than in the 18 with normal phase 3 slopes (P< .05). We conclude 1) groups of asthmatic children with and without persistent obstruction of peripheral airways can be identified by the single breath nitrogen washout and 2) those children with persistent obstruction of peripheral airways tend to be hypoxemic and have a relatively high incidence of status asthmaticus.

Pulmonary function and concentrations of alpha 1-antitrypsin and immunoglobulin E in workers exposed to pancreatic enzymes.

Fourteen workers exposed to pancreatic enzymes in tanneries were studied by interview, spirometry, and the single-breath nitrogen washout technique. Blood concentrations of alpha 1-antitrypsin and immunoglobulin E (IgE) were determined. For each exposed subject a nonexposed referent was selected, matched by sex, age, height and smoking habits. Symptoms in the airways were reported by four of the 14 subjects when weighing pancreatic enzymes. The exposed group did not show any deterioration in pulmonary volumes, forced expiratory flow, airway closure, or gas distribution when compared to the referents. The exposed group had significantly higher plasma levels of alpha 1-antitrypsin than the referents. This elevation might be a compensatory response to increased levels of proteases within the lungs. The serum levels of IgE did not differ between the groups.

Exposure to terpenes: effects on pulmonary function.

Forty-eight subjects exposed to terpenes (mean air concentration 258 mg m-3) and 47 unexposed subjects, all employed at sawmills, were studied with regard to symptoms and pulmonary function. Dyspnoea and chest oppression were significantly increased in the exposed subjects compared to the unexposed controls. A reduced FEV1, on spirometry and an increased CV% and slope of the alveolar plateau (phase III) on single breath nitrogen washout were seen on Monday morning before exposure to terpenes. There was no correlation between exposure time (duration of employment) and lung function impairment. A day of industrial exposure to terpenes caused no further change in any lung function variable. The unexposed controls showed normal spirometry and nitrogen washouts. The findings indicate a slight stable lung function impairment of an obstructive nature which does not necessarily undergo further deterioration with increased duration of exposure.

Functional classification of chronic airflow limitation based on flow-volume and single-breath nitrogen washout criteria.

A simple means of functional classification of the individual patient has been devised. The performance of a forced flow-volume manoeuvre in concert with a single-breath nitrogen washout procedure in 54 comprehensively investigated patients with chronic airflow limitation yielded two parameters which could be employed in classification. A normalized alveolar nitrogen slope (FEV1/FVC X delta N2%) greater than 4.0% per litre clearly delineated emphysema. The peak flow ratio (PEFR/PIFR%) categorized other subgroupings: a value in excess of 100% strongly suggests primary bronchial disease, while a lower value almost certainly indicates a mixed functional disorder.

The effects of intravenous infusion of saline on lung density, lung volumes, nitrogen washout, computed tomographic scans, and chest radiographs in humans.

In this study we examined the effect of a 15% increase in extracellular fluid volume on lung density, lung volumes, nitrogen washout, chest radiographs and computerized tomographic (CT) scans of the thorax in 5 volunteers. The objective of the study was to determine the sensitivity of these techniques in detecting small changes in lung water. Lung density was measured by a gamma ray Compton scatter technique and with an Ohio nuclear delta 2020 CT scanner. We measured or derived functional residual capacity, residual volume (RV), vital capacity (VC), and total lung capacity by helium dilution. Single-breath nitrogen washout was used to measure closing volume and the slope of phase III nitrogen washout (delta N2). Chest radiographs were taken in the posteroanterior and lateral projections. With the CT scanner we obtained slices 1 cm thick through the bases of the lungs and at 6 and 12 cm up from the bases. All these measurements were made before and 20 to 90 min after the intravenous infusion of 30 ml/kg body weight of warm saline over a period of 20 min. The most striking findings were a 24% increase in delta N2, a 14% increase in RV, and a 4.5% decrease in VC. Chest radiographs and the CT scans showed an increase in the size of the azygos veins. There was no change in Compton scatter density or the CT numbers. These results suggest that (1) tests of small airway function, such as RV and delta N2, are more sensitive than radiographic techniques to small increases in lung water, (2) there is some protection of the lung to increases in extracellular fluid volume.

Immediate Effect of Cigarette Smoking on the Maximal Expiratory Flow-Volume Curve and Single Breath Nitrogen Washout Test

Immediate Effect of Cigarette Smoking on the Maximal Expiratory Flow-Volume Curve and Single Breath Nitrogen Washout Test

Exposure to formaldehyde: effects on pulmonary function.

Forty-seven subjects exposed to formaldehyde (mean air concentration 0.45 mg/m3) and 20 unexposed subjects, all of whom were employed at a carpentry shop, were studied with regard to symptoms and pulmonary function. Symptoms involving eyes and throat as well as chest oppression were significantly more common in the exposed subjects than in the unexposed controls. Spirometry and single breath nitrogen washout were normal Monday morning before exposure to formaldehyde. A reduction in forced expiratory volume in 1 sec by an average of 0.2 L (P = .002), percent forced expiratory volume by 2% (P = .04), maximum midexpiratory flow by 0.3 L/sec (P = .04) and an increase in closing volume in percentage of vital capacity by 3.4% (P - .002) were seen after a day of work and exposure to formaldehyde, suggesting bronchoconstriction. Smokers and nonsmokers displayed similar changes in spirometry and nitrogen washout.

Wheezing, asthma, and pulmonary dysfunction 10 years after infection with respiratory syncytial virus in infancy.

Of the 180 children admitted to hospitals in Tyneside in the first year of life with proved respiratory syncytial virus lower respiratory tract infection, 130 were seen for review 10 years later and 34 of the remaining 50 children accounted for. Skin tests, lung function tests, and histamine-challenge and exercise tests for bronchial lability were undertaken in over 100 of the index children and a similar number of control children. A total of 55 (42%) of the 130 index children had had further episodes of wheeze, while only 21 (19%) out of 111 controls had ever wheezed; but few (6.2% v 4.5%) had troublesome symptoms at the age of 10. There was a threefold increase in the incidence of bronchial lability in the index children but no excess of atopy. Maximum expiratory air flow was reduced throughout the vital capacity manoeuvre in the index children, even when those with a history of recurrent wheeze were excluded. Results of single-breath nitrogen washout tests were normal, however, suggesting that ventilation was not appreciably uneven, even though expiratory flow was restricted. These differences might have been caused by infection damaging the growing lung but might also be explained by pre-existing differences in the airway, rendering certain children more susceptible to symptomatic infection when first challenged by the virus in infancy.

Airway closure and distribution during hip arthroplasty.

Airway closure, resting lung volume (FRC) and gas distribution were assessed single breath nitrogen washout during hip arthroplasty. Airway closure occurred above FRC in all the patients during enflurane anaesthesia and surgery, with no change in either FRC or airway closure when the femoral and acetabular prostheses were inserted. The slope of the nitrogen alveolar plateau, which was considered to indicate gas distribution, rose significantly from 4.1 to 5.7% N2/1 when the prostheses were inserted. By the end of surgery the slope had returned to the initial value. This finding indicates a transient effect on the airways when the prostheses are implanted.

The chest radiograph in chronic obstructive lung disease compared with measurements of single-breath nitrogen washout and spirometry

Postero-anterior and lateral chest radiographs were taken in 56 patients with chronic obstructive lung disease in whom the forced expiratory volume (FEV1), total lung capacity (TLC), the residual volume (RV) and the slope of phase III (S3) on the single breath nitrogen washout test (SBN2) were known. The shape and the level of the diaphragm and the shape of the costophrenic sulci, were determined from the chest films and were found to correlate with S3 and FEV1 but not TLC or RV/TLC%.

Single breath nitrogen washout in pulmonary sarcoidosis.

In 35 patients with pulmonary sarcoidosis we explored the utility of single breath nitrogen washout as a means for detecting abnormalities in airway function and intrapulmonary distribution of air. Closing volume/vital capacity ratio (CV/VC) was 21% (predicted 12.5%) in patients with only hilar adenopathy (stage I). CV/VC was 21% (predicted 13%) in patients with hilar adenopathy and parenchymal infiltration (stage II). Abnormalities in CV/VC were less readily detectable in patients with parenchymal infiltrates only (stage III) or those with bullous lesions and lung retraction (stage IV). Closing capacity was abnormally high in 66% of the cases. The slope of the alveolar plateau (delta N2/L) increased with disease progression. Single breath nitrogen test provides useful information concerning the function of small airways and distribution of pulmonary ventilation in all stages of sarcoidosis.

Effect of systemic venous hypertension on pulmonary function and lung water

We studied the effects of systemic venous hypertension (SVH) of 25 cmH2O, with and without fluid overload (100 ml.kg-1.h-1 x 4 h), on the lung water content and pulmonary function of anesthetized dogs. SVH was produced by inflating a balloon in the right atrium. Pulmonary extravascular water (PEW) was measured by gravimetric techniques taking the water content of trapped blood into consideration. Subdivisions of lung volume, pulmonary resistance, dynamic compliance, and the single-breath nitrogen washout curve were performed in a body plethysmograph. Vascular pressures, serum oncotic pressure, and arterial blood gases were also measured. Systemic venous hypertension alone produced no change in lung water content (control PEW = 3.46 +/- 0.16; SVH PEW = 3.44 +/- 0.18 g H2O/g dry tissue, mean +/- SD) or alterations in pulmonary function. Fluid overload alone produced an insignificant increase in PEW (4.24 +/- 0.72 g H2O/g dry tissue) and decreases in vital capacity and functional residual capacity. SVH in combination with fluid overload resulted in a significant increase in lung water (4.78 +/- 1.03 g H2O/g dry tissue) and decreases in functional residual capacity, vital capacity, dynamic compliance, and arterial blood oxygen tension as well as increased pulmonary resistance. We conclude that SVH favors the formation of pulmonary edema under conditions of increased pulmonary transcapillary fluid exchange and may particularly augment airway edema.

Intrasubject variability of pulmonary function testing in healthy children.

The intrasubject variability of repeat pulmonary function testing was examined in 20 healthy children aged 10 to 16 years. The children were tested a maximum of 11 times over a period of two months. The tests examined were spirometry, maximum expiratory flow-volume curves, body plethysmograph determination of lung volumes, and single breath nitrogen washout. The time of day or the length of the re-test interval, up to a period of two months, did not significantly affect the variability. Standard deviation was used when comparing the variability of measurements with the same units and coefficient of variation was used when comparing measurements of different units. The vital capacity measured by spirometry was the least variable measurement. Functional residual capacity, residual volume and total lung capacity were equally reproducible but as a group were more variable than vital capacity. There was no significant difference between the variability of the following measurements: forced expired flow from 25 to 75% of the vital capacity, flows at 70%, 50% and 40% total lung capacity, and flows at 50% vital capacity. Flows at 25% vital capacity were significantly less variable than other measurements of flow. The variability of forced expired volume in one second was examined and the use of this measurement in determining significant bronchial hyper-reactivity was assessed.

Collateral ventilation in excised human lungs.

Pressure-volume (PV) curves and single-breath nitrogen (SBN) washout traces were obtained in 32 excised human lungs. Comparison of the volumes at the onset of phage IV of the SBN traces (V phase IV) and the volumes at the inflection points (VIP) of the PV curves revealed V phase IV to be significantly larger than VIP. We postulated that V phase IV was caused by bulk airway closure and that the difference between V phase IV and VIP was due to collateral ventilation. To test this we correlated V phas IV -- VIP with age and emphysema grades of the lungs. Significant correlations were obtained, demonstrating that with increasing age and emphysema grade V phase IV -- VIP also increased. This is consistent with the documented evidence for decreased resistance to collateral ventilation with increasing age and emphysema. In addition, in a total of 86 lungs we demonstrated that with increasing age and emphysema there is an increasing incidence of total lack of sigmoid deviation in the PV curve.

Airway closure in each lung of anesthetized human subjects.

Airway closure and functional residual capacity (FRC) were assessed for each lung separately in the anesthetized subject by means of a double-lumen tracheal catheter. Airway closure was studied by argon-bolus and nitrogen-washout techniques, and FRC was calculated from single-breath nitrogen washout. Recordings were done with subjects in the supine and lateral postures. In the supine position, closing capacity (CC) exceeded FRC in each lung. Airway closure occurred synchronously in the two lungs. Argon CC was 0.05-0.1 liter larger than nitrogen CC of either lung. Minor gas trapping occurred during the vital capacity (VC) maneuver, so that inspired VC exceeded expired VC by 3%. In the left lateral posture, CC remained unaltered in either lung, whereas FRC was markedly increased in the nondependent and reduced in the dependent lung. Airway closure occurred asynchronously in the two lungs, and its distribution was discontinuous between them. Onset of airway closure in the dependent lung caused an early (60% VC) upstroke on the overall tracer gas recording (sampling of mixed expirate at the mouth), whereas onset of airway closure in the nondependent lung caused an additional upstroke at 10% VC. Gas trapping was more marked in the dependent lung than in the supine position, but some gas was released (expired VC greater than inspired VC) n the nondependent lung.

Effects of intercostal nerve blocks on pulmonary mechanics in healthy men.

Bilateral block of the 5th through the 11th intercostal nerves was induced in 16 healthy men. In eight of the men, bupivacaine 0.25% was used and in the other eight, etidocaine 0.5%. Before and after induction of the block flow/volume curves, maximal airway pressures, and pulmonary compliance, were recorded, and helium spirometry and multiple and single breath nitrogen wash-outs were performed. There were no differences between the results in the two groups, and the material was therefore pooled. Total lung capacity was decreased by 4%. There was no increase in residual volume, though the maximal expiratory airway pressure decreased by 7%. There was an 8% decrease in functional residual capacity. Pulmonary recoil appeared to be unchanged, as also did the effort-independent peak expiratory flow rates. According to the pulmonary nitrogen clearance index, the overall pulmonary time constant did not alter, while the slope of the alveolar plateau in the single breath nitrogen wash-out test increased by 9%. The significance of the latter finding is unclear, but it is concluded that the nerve block had no obvious effects on pulmonary mechanics, the changes observed rather being attributable to effects on the chest wall.

A network theory of bronchial gas mixing applied to single breath nitrogen washout.

A purely convective network theory of lung washout is developed and applied to analyze the standard single breath N2 washout test. The theory shows that if convective mixing only is assumed during washout, it is always possible to describe the washout curve as the output from an equivalent symmetric bronchial tree plus a presumably small remainder term due to asymmetry. By using this theory, Weibel’s and Horsfield and Cummings’ models of bronchial anatomy, and the assumption that a steady state N2 concentration profile is washed out, an estimate is obtained of the number and total cross section of the alveolar ducts contributing gas to the alveolar plateau. This estimate agrees well with anatomical estimates and suggests that the theory can be useful in obtaining information about peripheral airways in living subjects. It is also shown in a qualitative manner how the theory can account for cardiogenic oscillations superimposed on phase III of the single breath N2 washout curve. The theory can be generalized to include the effects of a complete asymmetric airway geometry and unsteady bronchial flow; however, at the present time, insufficient physiological data are available to analyze the most general convective washout problem.

The UCLA Population Studies of Chronic Obstructive Respiratory Disease: 3. Comparison of Pulmonary Function in Three Communities Exposed to Photochemical Oxidants, Multiple Primary Pollutants, or Minimal Pollutants

The respiratory status of residents of three areas exposed to (1) photochemical oxidants (Burbank, Calif), (2) sulfur dioxide, particulates, and hydrocarbons (Long Beach, Calif), and (3) low levels of pollutants (Lancaster, Calif) was determined using a modified National Heart and Lung Institute questionnaire, electronic volume spirometric studies, the single-breath nitrogen washout test, and body plethysmographic studies. Each area under study was within 2 km of a monitoring station of the Southern California Air Quality Management District. Seventy to 79 percent of the residents of enumerated households completed testing. Results of retesting a 3 percent probability sample at the Pulmonary Function Laboratory of the University of California, Los Angeles, indicated reasonable repeatability for all tests except the single-breath nitrogen test. Among the three areas, participants from Lancaster, Calif (low pollution), had the greatest number of "best" performance values and the least number of "worst" performance values for the tests. The distribution of best and worst performance among the three areas was similar for current smokers, those who had never smoked, and all participants for each of the tests. Mean test values of dysfunction of the small airways were either slightly better (single-breath nitrogen test) in the two polluted areas or similar (maximal expiratory flow rates at 50 percent and at 75 percent of forced vital capacity below total lung capacity) in all three areas. Mean plethysmographic values (thoracic gas volume, airway resistance, and specific airway resistance) were "worst" in participants from Burbank, Calif (photochemical oxidants); and spirometric values were "worst" in participants from Long Beach, Calif (sulfur dioxide, particulates, and hydrocarbons). Within the limitations of the cross-sectional study design, the results suggest that residence in the two polluted areas is associated with respiratory impairment, primarily of functions of the large airways.

Pulmonary Function Abnormalities in Thalassemia Patients on a Hypertransfusion Program

Pulmonary function tests were performed in 12 thalassemia patients on a hypertransfusion program (age 18.4 +/- 2.6 SEM years) to determine the presence of any abnormalities of lung function. These included spirometry, expiratory flow rates, body plethysmography, single-breath nitrogen washout, single breath carbon monoxide diffusing capacity, and arterial blood gases. Only one patient had normal pulmonary function. Arterial hypoxemia was present in ten of 12 patients at rest. The total lung capacity (TLC) was normal. The residual volume was abnormally increased in five of 12 patients. The slope of phase III of single breath nitrogen washout curve was abnormal in five of 12 patients, but the closing volume was normal. The maximal expiratory flow rate at 60% total lung capacity was decreased in four of 12 patients, suggesting the presence of small airway disease. The single breath carbon monoxide diffusing capacity was normal in all patients. These pulmonary function abnormalities did not correlate with age or the cumulative amount of iron via blood transfused. The small airway obstruction, hyperinflation; and hypoxemia observed in thalassemia patients on a hypertransfusion program may result from the basic disease, iron deposition in the lungs, or other factors.

Airway Responses in Normal Subjects following Topical Anesthesia with Ultrasonic Aerosols of 4% Lidocaine

Airway dynamics were studied in seven healthy unanesthetized male subjects before and after topical anesthesia with ultrasonic aerosols of 4% lidocaine to assess the effects of this clinically useful technique on normal pulmonary function. Responses to the ultrasonic mist per se were evaluated by studies on separate days with physiologic saline. Significant increases in expiratory flow rates during maximal and partial expiratory flow-volume curves occurred in response to lidocaine. In contrast, flows during partial expiratory flow-volume curves were reduced following saline inhalation. Lung elastic recoil was unaffected by either aerosol. Results of single breath nitrogen washout and responses to breathing helium were unchanged following topical anesthesia with lidocaine, but the saline aerosol significantly increased the slope of phase III during nitrogen washout and volume of isoflow after breathing helium. These changes indicate that topical anesthesia of the airway with 4% lidocaine given as an ultrasonic aerosol produces mild bronchodilation in healthy subjects, whereas saline administered in the same fashion causes mild bronchoconstriction. The effects of both aerosols most likely represent direct action on the smaller peripheral bronchi.