Pulmonary function changes following helical tomotherapy in patients with inoperable, locally advanced non-small cell lung cancer.

PURPOSE: To evaluate alterations in pulmonary function indices after helical tomotherapy and explore potential associations with biologically corrected dosimetric parameters. PATIENTS AND METHODS: In 64 patients with inoperable locally advanced non-small cell lung cancer, pulmonary function tests before and within 6 months after radiotherapy were evaluated retrospectively. In the case of concurrent chemotherapy a total dose of 67.2 Gy was delivered, otherwise 70.5 Gy was provided. In 44 patients, late pulmonary function changes (≥6 months after radiotherapy) could also be assessed. RESULTS: In the entire patient group, there were significant declines in forced expiratory volume in 1s (FEV1) (average change -4.1% predicted; P = 0.007), in forced vital capacity (FVC) (-4.9% predicted; P = 0.002), total lung capacity (TLC) (-5.8% predicted; P = 0.0016) and DLCO (diffusing capacity of the lung for carbon monoxide corrected for hemoglobin level) (-8.6% predicted; P < 0.001) during the first 6 months. Corresponding FEV1, FVC, TLC and DLCO declines in the subgroup with late measurements (after 11.3 months on average) were -5.7, -7.4, -7.0, -9.8% predicted. A multivariate analysis including V5 Gy, V10 Gy, V20 Gy, V40 Gy, V60 Gy, mean lung dose (MLD), gross tumor volume (GTV) and planning target volume (PTV) as potential covariates showed that GTV was the most consistent contributor, being significant for ∆FEV1 (P = 0.003), ∆FVC (P = 0.003), ∆TLC (P = 0.001) and ∆DLCO (P = 0.01). V5 Gy or V10 Gy did not contribute to any of the lung function changes. CONCLUSIONS: The decline in pulmonary function indices after helical tomotherapy was of similar magnitude to that observed in studies reporting the effect of conformal radiotherapy on lung function. Diffusion capacity was the parameter showing the largest decrease following radiation therapy as compared to baseline and correlated with gross tumor volume. None of the alterations in pulmonary function tests were associated with the lung volume receiving low-dose radiation.

Impact of a single 10 min education session on asthma control as measured by ACT.

BACKGROUND: Aim: Despite the availability of effective treatments for asthma, many patients still suffer from uncontrolled asthma. This study evaluates whether a single educational session could improve asthma control assessed by Asthma Control Test (ACT) score as well as knowledge of the inhaler device, knowledge of medication and inhalation technique. METHODS: This prospective single blinded randomized controlled trial of 160 adults with asthma, examined the effectiveness of a single standardized, educational intervention, performed by a respiratory nurse specialist. The education provided to the intervention group consisted of basic information about asthma treatment and instructions on inhalation technique for about 10min. This additional education was not offered to the control group. In both groups ACT scores, knowledge of medication, knowledge of inhaler device and inhalation technique were assessed at baseline and after three months. Asthma was considered well-controlled when the ACT score exceeded 19. RESULTS: At baseline there were no significant differences in patient demographics, degree of asthma control, knowledge of medication or device and inhalation technique between the intervention group and the control group. In the intervention group the educational session resulted in a significantly higher proportion of well-controlled asthma patients with an ACT>19 (43% versus 77%) (p < 0.001) after three months. In the control group this proportion remained similar (57% versus 67%) (p > 0.1). We also observed improvements in knowledge of medication (p < 0.001), knowledge of device (p < 0.001) and inhalation technique (p = 0.004) in the intervention group and not in the control group. CONCLUSION: A single 10 min, educational session provided by a respiratory nurse specialist can substantially improve asthma control determined by the ACT score after three months.

Increase in ventilated air spaces after eradication of chronic methicillin-resistant Staphylococcus aureus infection in cystic fibrosis patients.

Effective microbiogical eradication of methicillin-resistant Staphylococcus aureus (MRSA) in patients with cystic fibrosis (CF) can be obtained, but its effect is not always clear-cut in terms of spirometric indices. The aim of this observational prospective cohort study was to study the potential effect of eradication of chronic MRSA infection on lung function including ventilation distribution. Six CF patients, chronically colonized with MRSA (median age: 21 years (range 14-46); median FEV1: 76 (95%CI 58-98)%pred) were successfully eradicated using oral rifampicin and fusidic acid in combination with topical decolonization measures. Lung function and multiple breath washout test were performed at the start and at the end of the eradication protocol and after an average follow-up period of 7·5±1·5(SD) months. One patient cultured MRSA again 4 months after successful eradication. All patients reported reduced sputum production and viscosity. By the end of the follow-up period, there was an increase in ventilated FRCMBW and no change in plethysmographic FRCPL. This resulted in a significant decrease of trapped air by half a litre (from 579 to 40 ml; P = 0·013). Lung clearance index (LCI) also showed a small but significant decrease (from 7·2 to 6·7; P = 0·014) after eradication of MRSA. We conclude that MRSA eradication can be successful, also in terms of recruitment of previously unventilated air spaces, potentially due to reduced sputum production and/or viscosity.

Whole-lung lavage: a successful treatment for restoring acinar ventilation distribution in primary acquired pulmonary alveolar proteinosis.

A 51-year-old active smoker with primary acquired pulmonary alveolar proteinosis (PAP) diagnosed by biopsy and anti-GM-CSF antibodies was treated safely with whole-lung lavage (WLL). This resulted in a rapid improvement of symptoms and arterial blood oxygenation, but not of standard lung function parameters. However, we also performed the multiple-breath nitrogen washout (MBW) test to determine the lung clearance index (LCI) as well as indices of acinar ventilation heterogeneity (S(acin)) and conductive ventilation heterogeneity (S(cond)). At baseline, a distinct abnormality was seen for S(acin) and LCI, while S(cond) was at the upper limit of normal for this subject. S(acin), in particular, was in excess of the S(acin) abnormality corresponding to a 20-pack-year smoking history. Immediately after WLL, S(acin) and S(cond) both fell to within a normal range while LCI also decreased but remained abnormal. The S(acin) decrease was much greater than the S(cond) decrease, which was to be expected after 1 week of smoking cessation at the hospital (smoking was resumed after release from hospital). A follow-up visit 7 weeks after WLL revealed a spectacular improvement on CT scan and improvements in standard lung function. Another follow-up visit 14 weeks after WLL showed further improvements in standard lung function, and both S(acin) and S(cond) remained well within the normal range, and LCI was above the upper limit of normal. We conclude that in this patient, removal of excess surfactant by WLL resulted in a restored ventilation distribution in most of the distal air spaces.

[Functional measurements of the peripheral airways in COPD]. / Explorations fonctionnelles respiratoires des voies aériennes distales dans la BPCO.

INTRODUCTION: COPD is characterized by airflow limitation that is not fully reversible. Changes in the structure and function of the small airways (less than 2mm diameter) are now recognized to play a major pathophysiological and mechanical role in airflow limitation in COPD. There is, therefore, a need for technology to quantify small airways disease. BACKGROUND: For the diagnosis and assessment of COPD, spirometry is the gold standard (postbronchodilator FEV(1)/FVC less than 70%). The ATS/ERS definition of an obstructive pulmonary defect contrasts with the definitions suggested by clinical guidelines, in that FEV(1) is related to VC rather than FVC and the cut-off value of this ratio is set at the 5(th) percentile of the normal distribution rather than at a fixed value of 0.7. There is also a significant association between the severity of the disease and the degree of inflammation in the small airways. Therefore, a variety of physiological tests have been proposed as non-invasive surrogate measurements of distal lung function, such as a reduction in the forced expiratory flow at 25% to 75% of forced vital capacity (FEF(25-75)). However, the reproducibility and comparability of the FEF(25-75) is limited if not adjusted for lung volume, and the relationship between FEF(25-75) and histology is unknown. It is difficult to quantify the narrowing of the small airways and physiological measurements are difficult to interpret because there is abnormal airflow in the larger airways. Therefore, it will be difficult to assess the effects of new treatments on small airway function, and it is important to develop new techniques in order to do so. VIEWPOINT: The single breath nitrogen washout, with calculation of the slope (dN(2)) of the N(2) alveolar plateau, the closing volume and the closing capacity, is a more sensitive test of early lung damage in smokers than the FEV(1). The Forced Oscillation Technique (FOT) is a method for assessing respiratory mechanics non-invasively during spontaneous breathing. The more sophisticated multiple breath washout test (MBW) has the potential to locate the affected small airways anatomically in acinar and conductive lung zones through increased phase III slope indices, Sacin and Scond. In more advanced stages of smoking-induced lung disease, differential patterns of Sacin and Scond are characteristics of parenchymal destruction in addition to peripheral airways changes. CONCLUSION: These functional tests are promising solutions for small airways assessment. FOT has the advantage of being a simple method, requiring only the passive cooperation of the subject.

Prevalence and impact on FEV(1) decline of chronic methicillin-resistant Staphylococcus aureus (MRSA) colonization in patients with cystic fibrosis. A single-center, case control study of 165 patients.

BACKGROUND: Risk factors for methicillin-resistant Staphylococcus aureus (MRSA) in Cystic Fibrosis (CF) and the impact on CF disease progression are still under debate. The objectives of this study were to determine clinical variables associated with MRSA colonization and examine impact on FEV(1) evolution in CF patients. METHODS: A retrospective case-control study using the University Hospital of Brussels CF clinic patient registry from 2002 to 2010, comparing clinical variables and decline of FEV(1) of MRSA positive patients with age and sex matched controls, chronically colonized with S. aureus. RESULTS: Thirty of the 165 CF patients, chronically colonized with S. aureus, had cultures positive for MRSA (18.2%). Excluding patients under 4 years, the prevalence became 15.2% (23/151). Chronic colonization (i.e., three or more consecutive positive cultures) was found in 19/151 (12.6%). The MRSA positive group showed a higher proportion of patients with genotype F508del, less pancreas sufficient patients, more bronchiectasis and more frequent hospitalization. The FEV(1) recorded one year prior to, and at the moment of MRSA acquisition, was lower but not significantly different from that obtained in controls (72.9%±26.6 vs 84.3±21.8 and 68.2%±27.1 vs 81.4%±24.3 respectively, p>0.1). However, FEV(1) decline over 2- and 6-year periods, were significantly greater in the chronic MRSA group than in the controls (-5%±5.5 vs -2.5±2.3 over 2 years (p=0.043) and -1.8%±4.6 vs -1.0%±1.9 over a 6-year period (p=0.026)). CONCLUSION: In our center the prevalence of MRSA in CF patients, chronically colonized with S. aureus and over the age of 4 years, was 15.2% (12.6% chronic infection). MRSA colonization was shown to be associated with a genotype F508del, presence of bronchiectasis and hospitalization. Our spirometric data also show that a MRSA episode entails an FEV(1) decline that is almost double that predicted for CF patients who can remain unaffected by MRSA.

Update on the roles of distal airways in COPD.

This review is the summary of a workshop on the role of distal airways in chronic obstructive pulmonary disease (COPD), which took place in 2009 in Vence, France. The evidence showing inflammation and remodelling in distal airways and the possible involvement of these in the pathobiology, physiology, clinical manifestations and natural history of COPD were examined. The usefulness and limitations of physiological tests and imaging techniques for assessing distal airways abnormalities were evaluated. Ex vivo studies in isolated lungs and invasive measurements of airway resistance in living individuals have revealed that distal airways represent the main site of airflow limitation in COPD. Structural changes in small conducting airways, including increased wall thickness and obstruction by muco-inflammatory exudates, and emphysema (resulting in premature airway closure), were important determinants of airflow limitation. Infiltration of small conducting airways by phagocytes (macrophages and neutrophils), dendritic cells and T and B lymphocytes increased with airflow limitation. Distal airways abnormalities were associated with patient-related outcomes (e.g. dyspnoea and reduced health-related quality of life) and with the natural history of the disease, as reflected by lung function decline and mortality. These data provide a clear rationale for targeting distal airways in COPD.

Inspiratory and expiratory aerosol deposition in the upper airway.

Aerosol deposition efficiency (DE) in the extrathoracic airways during mouth breathing is currently documented only for the inspiratory phase of respiration, and there is a need for quantification of expiratory DE. Our aim was to study both inspiratory and expiratory DE in a realistic upper airway geometry. This was done experimentally on a physical upper airway cast by scintigraphy, and numerically by computational fluid dynamic simulations using a Reynolds Averaged Navier?Stokes (RANS) method with a k-? SST turbulence model coupled with a stochastic Lagrangian approach. Experiments and simulations were carried out for particle sizes (3 and 6 µm) and flow rates (30 and 60 L/min) spanning the ranges of Stokes (Stk) and Reynolds (Re) number pertinent to therapeutic and environmental aerosols. We showed that inspiratory total deposition data obtained by scintigraphy fell onto a previously published deposition curve representative of a range of upper airway geometries. We also found that expiratory and inspiratory DE curves were almost identical. Finally, DE in different compartments of the upper airway model showed a very different distribution pattern of aerosol deposition during inspiration and expiration, with preferential deposition in oral and pharyngeal compartments, respectively. These compartmental deposition patterns were very consistent and only slightly dependent on particle size or flow rate. Total deposition for inspiration and expiration was reasonably well-mimicked by the RANS simulation method we employed, and more convincingly so in the upper range of the Stk and Re number. However, compartmental deposition patterns showed discrepancies between experiments and RANS simulations, particularly during expiration.

Forced vital capacity and forced expiratory volume in six seconds as predictors of reduced total lung capacity.

The present study aims to derive guidelines that identify patients for whom spirometry can reliably predict a reduced total lung capacity (TLC). A total of 12,693 lung function tests were analysed on Caucasian subjects, aged 18-70 yrs. Restriction was defined as a reduced TLC. Lower limits of normal (LLN) for TLC were obtained from the European Respiratory Society recommended reference equations. Reference equations from the National Health and Nutrition Examination Survey III were used for forced vital capacity (FVC) and forced expiratory volume in six seconds (FEV(6)). The performance of FVC and FEV(6) to predict the presence of restriction was studied as follows: 1) using two-by-two (2x2) tables; and 2) by logistic regression analysis. Both analyses were performed in obstructive (defined as forced expiratory volume in one second (FEV(1))/FVC or FEV(1)/FEV(6) 100% pred (males) or >85% pred (females). In obstructive patients, spirometry cannot reliably diagnose a concomitant restrictive defect, but it can rule out restriction for patients with forced vital capacity or forced expiratory volume in six seconds >85% pred (males) or >70% pred (females).

Chest physiotherapy in cystic fibrosis: short-term effects of autogenic drainage preceded by wet inhalation of saline versus autogenic drainage preceded by intrapulmonary percussive ventilation with saline.

BACKGROUND: Chest physiotherapy has been used for many years to assist in the removal of abnormal viscid bronchial secretions in cystic fibrosis (CF) patients. OBJECTIVES: This study compared the short-term effects of two physiotherapy regimens in patients with CF: autogenic drainage (AD) preceded by either saline inhalation ('saline(NEB) + AD') or by intrapulmonary percussive ventilation (IPV) with saline ('saline(IPV) + AD'). METHODS: In a randomized crossover design, 20 clinically stable CF patients with similar pulmonary function at baseline received either 'saline(NEB) + AD' or 'saline(IPV) + AD' on 2 consecutive days. Transcutaneous oxygen saturation, heart rate, Borg dyspnea score and mucus wet weight were evaluated after 15 min of either saline(NEB) or saline(IPV), and after a subsequent 30 min of AD. RESULTS: There were no significant changes in oxygen saturation, heart rate or Borg score at any point of either physiotherapy intervention. There was no significant difference in sputum wet weight recovered with either saline(NEB) (2.2 +/- 1.8 g, mean +/- SD) or saline(IPV) (1.7 +/- 1.9 g) alone. Subsequent AD did produce significantly greater amounts of sputum wet weight (p < 0.0001 for both) than in the initial saline delivery period, yet the amount of wet weight was similar irrespective of whether AD was preceded by saline(NEB) (9.7 +/- 6.5 g) or saline(IPV) (11.6 +/- 7.3 g). CONCLUSIONS: Recovered sputum weight is similar whether AD is preceded by saline(NEB) or saline(IPV). The much greater amount of mucus obtained during the AD period than during the saline delivery period warrants further investigation.

Influence of glottic aperture on the tracheal flow.

The extra-thoracic mouth-throat area has a major influence on the aerosol delivery to the proximal or peripheral intra-thoracic airways. To characterize the particle deposition in this area, it is important to investigate first the flow structures in this crucial--in relation to the aerosol deposition--region. The glottis, which is delimited by the vocal cords and therefore has the narrowest passage, generates a laryngeal jet and a reverse flow downstream the glottis. It is generally assumed that the glottis has different shapes and cross-sectional areas at different moments during the respiratory cycle and also depends on the average inspiratory flow rate. Therefore, the influence of a circular glottal aperture, with a cross-sectional area of 90 mm2 and an elliptical and triangular shape, both with an area of 45 mm2, on the flow is investigated. However, the area of the circular aperture is twice as big as the area of the elliptical one, it has almost no influence on the flow structures. On the other hand, the triangular glottal aperture shifts the laryngeal jet in the direction of the posterior wall, and generates two pairs of counter rotating secondary vortices downstream the glottis, where the circular and elliptical only aperture generates one pair of vortices. The difference in pressure drop is more dominated by the cross-sectional area than by the shape of the glottis. This suggests the need for rendering geometry of future upper airway models even more realistic as the appropriate three-dimensional (3D) medical imaging techniques are becoming available.

Obstructive and restrictive spirometric patterns: fixed cut-offs for FEV1/FEV6 and FEV6.

The purpose of this study was to determine fixed cut-off points for forced expiratory volume in one second (FEV(1))/FEV(6) and FEV(6) as an alternative for FEV(1)/forced vital capacity (FVC) and FVC in the detection of obstructive and restrictive spirometric patterns, respectively. For the study, a total of 11,676 spirometric examinations, which took place on Caucasian subjects aged between 20-80 yrs, were analysed. Receiver-operator characteristic curves were used to determine the FEV(1)/FEV(6) ratio and FEV(6) value that corresponded to the optimal combination of sensitivity and specificity, compared with the commonly used fixed cut-off term for FEV(1)/FVC and FVC. The data from the current study indicate that FEV(1)/ FEV(6) <73% and FEV(6) <82% predicted can be used as a valid alternative for the FEV(1)/FVC <70% and FVC <80% pred cut-off points for the detection of obstruction and restriction, respectively. The statistical analysis demonstrated very good, overall, agreement between the two categorisation schemes. For the spirometric diagnosis of airway obstruction (prevalence of 45.9%), FEV(1)/FEV(6) sensitivity and specificity were 94.4 and 93.3%, respectively; the positive and negative predictive values were 92.2 and 95.2%, respectively. For the spirometric detection of a restrictive pattern (prevalence of 14.9%), FEV(6) sensitivity and specificity were 95.9 and 98.6%, respectively; the positive and negative predictive values were 92.2 and 99.3%, respectively. This study demonstrates that forced expiratory volume in one second/forced expiratory volume in six seconds <73% and forced expiratory volume in six seconds <82% predicted, can be used as valid alternatives to forced expiratory volume in one second/forced vital capacity <70% and forced vital capacity <80% predicted, as fixed cut-off terms for the detection of an obstructive or restrictive spirometric pattern in adults.

Music: a new cause of primary spontaneous pneumothorax.

Most cases of primary spontaneous pneumothorax are thought to be caused by air leaks at so-called "emphysema-like changes" or in areas of pleural porosity at the surface of the lung. Environmental pressure swings may cause air leaks as a result of transpulmonary pressure changes across areas of trapped gas in the distal lung. This is the first report of music as a specific form of air pressure change causing pneumothorax (five episodes in four patients). While rupture of the interface between the alveolar space and pleural cavity in these patients may be linked to the mechanical effects of acute transpulmonary pressure differences caused by exposure to sound energy in association with some form of distal air trapping, we speculate that repetitive pressure changes in the high energy-low frequency range of the sound exposures is more likely to be responsible. Exposure to loud music should be included as a precipitating factor in the history of patients with spontaneous pneumothorax.

Lower pulmonary diffusing capacity in the prone vs. supine posture.

We evaluated the effect of prone positioning on gas-transfer characteristics in normal human subjects. Single-breath (SB) and rebreathing (RB) maneuvers were employed to assess carbon monoxide diffusing capacity (DlCO), its components related to capillary blood volume (Vc) and membrane diffusing capacity (Dm), pulmonary tissue volume (Vti), and cardiac output (Qc). Alveolar volume (Va) was significantly greater prone than supine, irrespective of the test maneuver used. Nevertheless, Dl(CO) was consistently lower prone than supine, a difference that was enhanced when appropriately corrected for the higher Va prone. When adequately corrected for Va, diffusing capacity significantly decreased by 8% from supine to prone [SB: Dl(CO,corr) supine vs. prone: 32.6 +/- 2.3 (SE) vs. 30.0 +/- 2 ml x min(-1) x mmHg(-1) stpd; RB: Dl(CO,corr) supine vs. prone: 30.2 +/- 2.2 (SE) vs. 27.8 +/- 2.0 ml x min(-1) x mmHg(-1) stpd]. Both Vc and Dm showed a tendency to decrease from supine to prone, but neither reached significance. Finally, there were no significant differences in Vti or Qc between supine and prone. We interpret the lower diffusing capacity of the healthy lung in the prone posture based on the relatively larger space occupied by the heart in the dependent lung zones, leaving less space for zone 3 capillaries, and on the relatively lower position of the heart, leaving the zone 3 capillaries less engorged.

Similar ventilation distribution in normal subjects prone and supine during tidal breathing.

Multiple-breath washout (MBW) tests, with end-expiratory lung volume at functional residual capacity (FRC) and 90% O(2), 5% He, and 5% SF(6) as an inspired gas mixture, were performed in healthy volunteers in supine and prone postures. The semilog plot of MBW N(2) concentrations was evaluated in terms of its curvilinearity. The MBW N(2) normalized slope analysis yielded indexes of acinar and conductive ventilation heterogeneity (Verbanck S, Schuermans D, Van Muylem A, Paiva M, Noppen M, and Vincken W. J App Physiol 83: 1907-1916, 1997). Also, the difference between SF(6) and He normalized phase III slopes was computed in the first MBW expiration. Only MBW tests with similar FRC in the prone and supine postures (P > 0.1; n = 8) were considered. Prone and supine postures did not reveal any significant differences in curvilinearity, N(2) normalized slope-derived indexes of conductive or acinar ventilation heterogeneity, nor SF(6)-He normalized phase III slope difference in the first MBW expiration (P > 0.1 for all). The absence of significant changes in any of the MBW indexes suggests that ventilation heterogeneity is similar in the supine and prone postures of normal subjects breathing near FRC.

Methacholine versus histamine: paradoxical response of spirometry and ventilation distribution.

We investigated the differential effect of histamine and methacholine on spirometry and ventilation distribution (where indexes S(cond) and S(acin) represent conductive and acinar ventilation heterogeneity; Verbanck S, Schuermans D, Van Muylem A, Noppen M, Paiva M, and Vincken W. J Appl Physiol 83: 1807-1816, 1997). Thirty normal subjects were challenged with cumulative doses of 6.52 micromol histamine and, on a separate day, with either 6.67 micromol methacholine (equal-dose group; n = 15) or 13.3 micromol methacholine (double-dose group; n = 15). Largest average forced expiratory volume in 1 s (FEV(1)) decreases or S(cond) increases obtained in either group were -9% and +286%, respectively; S(acin) remained unaffected at all times. In the equal-dose group, a smaller FEV(1) decline (P = 0.002) after methacholine was paralleled by a smaller S(cond) increase (P = 0.041) than with histamine. However, in the double-dose group, methacholine maintained a smaller FEV(1) decline (P = 0.009) while inducing a larger S(cond) increase (P = 0.006) than did histamine. The differential action of histamine and methacholine is confined to the conductive airways, where histamine likely causes the greatest overall airway narrowing and methacholine induces the largest parallel heterogeneity in airway narrowing, probably at the level of the large and small conductive airways, respectively. The observed ventilation heterogeneities predict a risk for dissociation between ventilation-perfusion mismatch and spirometry, particularly after methacholine challenge.

Saline aerosol bolus dispersion. I. The effect of acinar airway alteration.

We explored the possibility of using a saline aerosol for bolus dispersion measurements to detect peripheral airway alterations in smokers. Indexes of ventilation inhomogeneity in conductive (S(cond)) and acinar (S(acin)) lung zones, as derived from the multiple-breath N(2) washout (Verbanck S, Schuermans D, Van Muylem A, Noppen M, Paiva M, and Vincken W, J Appl Physiol 83: 1807-1816, 1997), were also measured. The saline bolus test consisted of inhaling 60-ml saline aerosol boluses to different volumetric lung depths (VLD) in the 1.1 liter volume above functional residual capacity. In the never-smoker group (n = 12), saline boluses showed bolus dispersion values consistent with normal values reported in the literature for 0.5- to 1-microm aerosols. In the smoker group (n = 12; 28 +/- 9 pack years, mean +/- SD), significant increases were seen on dispersion and skew of the most peripherally inhaled saline boluses (VLD = 800 ml; P < 0.05) as well as on S(acin) (P = 0.007) with respect to never-smokers. Shallow inhaled boluses (VLD = 200 ml) and S(cond) did not reveal any significant differences between smokers and never-smokers. This study shows the consistent response of two conceptually independent tests, in which both saline aerosol and gas-derived indexes point to a heterogeneous distribution of smoking-induced structural alterations in the lung periphery.

Saline aerosol bolus dispersion. II. The effect of conductive airway alteration.

In a companion study (Verbanck S, Schuermans D, Vincken W, and Paiva M, J Appl Physiol 90: 1754-1762, 2001), we investigated whether saline aerosol bolus tests could also be used to detect proximal, as opposed to peripheral, airway alterations. We studied 10 never-smokers before and after histamine challenge, obtaining, for various volumetric lung depths (VLD), saline bolus-derived indexes computed by discarding aerosol concentrations below either 50% of the exhaled bolus maximum (half-width, H) or below cutoffs ranging from 5 to 25% (standard deviation, sigma(5%)-sigma(25%)) and skew (sk(5)-sk(25%)). Multiple-breath N(2) washout-derived indexes of conductive (S(cond)) and acinar (S(acin)) ventilation inhomogeneity were also determined. After histamine, S(cond) significantly increased (P = 0.008) whereas S(acin) remained unaffected, indicating purely conductive airway alteration. Consistent with this observation, sk(5%) (or sk(25%)) was increased to the same extent at all VLD, and sigma(5%) was increased preferentially at low VLD. By contrast, H and sigma(25%) displayed preferential increases at high VLD, a pattern similar to that induced by peripheral alterations. The present work shows that proximal airway alteration can be reliably identified by saline bolus tests only if these include measurements at low and high VLD and if bolus dispersion is quantified as a standard deviation with a low cutoff.