Diagnostic Potential of Oscillometry: A Population-based Approach.

Rationale: Respiratory resistance (Rrs) and reactance (Xrs) as measured by oscillometry and their intrabreath changes have emerged as sensitive parameters for detecting early pathological impairments during tidal breathing. Objectives: This study evaluates the prevalence and association of abnormal oscillometry parameters with respiratory symptoms and respiratory diseases in a general adult population. Methods: A total of 7,560 subjects in the Austrian LEAD (Lung, hEart, sociAl, boDy) Study with oscillometry measurements (computed with the Resmon Pro FULL; Restech Srl) were included in this study. The presence of respiratory symptoms and doctor-diagnosed respiratory diseases was assessed using an interview-based questionnaire. Rrs and Xrs at 5 Hz, their inspiratory and expiratory components, the area above the Xrs curve, and the presence of tidal expiratory flow limitation were analyzed. Normality ranges for oscillometry parameters were defined. Measurements and Main Results: The overall prevalence of abnormal oscillometry parameters was 20%. The incidence of abnormal oscillometry increased in the presence of symptoms or diagnoses: 17% (16-18%) versus 27% (25-29%), P < 0.0001. All abnormal oscillometry parameters except Rrs at 5 Hz were significantly associated with respiratory symptoms/diseases. Significant associations were found, even in subjects with normal spirometry, with abnormal oscillometry incidence rates increasing by 6% (4-8%; P < 0.0001) in subjects with symptoms or diagnoses. Conclusions: Abnormal oscillometry parameters are present in one-fifth of this adult population and are significantly associated with respiratory symptoms and disease. Our findings underscore the potential of oscillometry as a tool for detecting and evaluating respiratory impairments, even in individuals with normal spirometry.

Reference equations for within-breath respiratory oscillometry in White adults.

BACKGROUND: within-breath analysis of oscillometry parameters is a growing research area since it increases sensitivity and specificity to respiratory pathologies and conditions. However, reference equations for these parameters in White adults are lacking and devices using multiple sinusoids or pseudorandom forcing stimuli have been underrepresented in previous studies deriving reference equations. The current study aims to establish reference ranges for oscillometry parameters, including also the within-breath ones in White adults using multi-sinusoidal oscillations. METHODS: White adults with normal spirometry, BMI≤30kg/m2, without a smoking history, respiratory symptoms, pulmonary or cardiac disease, neurological or neuromuscular disorders, and respiratory tract infections in the previous 4 weeks were eligible for the study. Study subjects underwent oscillometry (multifrequency waveform at 5-11-19Hz, Resmon PRO FULL, Restech Srl, Italy) in 5 centers in Europe and the USA according to international standards. The within-breath and total resistance (R) and reactance (X), the resonance frequency, the area under the X curve, the frequency dependence of R (R5-19), and within-breath changes of X (ΔX) were submitted to Lambda-Mu-Sigma models for deriving reference equations. For each output parameter, an AIC-based stepwise input variable selection procedure was applied. RESULTS: 144 subjects (age 20.8 - 86.3 years; height 146 - 193 cm; BMI 17.42 - 29.98 kg/m2; 56% females) were included. We derived reference equations for 29 oscillatory parameters. Predicted values for inspiratory and expiratory parameters were similar, while differences were observed for their limits of normality. CONCLUSIONS: We derived reference equations with narrow confidence intervals for within-breath and whole-breath oscillatory parameters for White adults.

Self-reported exercise-induced dyspnea and airways obstruction assessed by oscillometry and spirometry in adolescents.

BACKGROUND: Self-reported exercise-induced dyspnea (EID) is common among adolescents. Possible underlying pathologies are exercise-induced bronchoconstriction (EIB) and laryngeal obstruction (EILO). The forced oscillation technique (FOT) may evaluate exercise-induced changes in airway caliber. AIM: To investigate in adolescents the relationship between EID, EIB (post-exercise fall in forced expiratory volume in 1s (FEV1 )≥10%), EILO, and post-exercise challenge changes in FOT parameters. METHODS: One hundred and forty-three subjects (97 with EID) of 13-15 years old underwent a standardized exercise challenge with FOT measurement and spirometry repeatedly performed between 2 and 30 min post-exercise. EILO was studied in a subset of 123 adolescents. Subjects showing greater changes than the healthy subgroup in the modulus of the inspiratory impedance were considered FOT responders. RESULTS: EID-nonEIB subjects presented similar post-exercise changes in all FOT parameters to nonEID-nonEIB adolescents. Changes in all FOT parameters correlated with FEV1 fall. 45 of 97 EID subjects responded neither by FEV1 nor FOT to exercise. 19 and 18 subjects responded only by FEV1 (onlyFEV1 responders) or FOT (onlyFOTresponders), respectively. Only a lower baseline forced vital capacity (FVC)%predicted and a higher FEV1 /FVC distinguished the onlyFEV1 responders from onlyFOTresponders. FOT parameters did not present specific post-exercise patterns in EILO subjects. CONCLUSION: FOT can be used to identify post-exercise changes in lower airway function. However, EID has a modest relation with both FEV1 and FOT responses, highlighting the need for objective testing. More research is needed to understand whether onlyFEV1 responders and onlyFOTresponders represent different endotypes.

Effects of Air Stacking on Dyspnea and Lung Function in Neuromuscular Diseases.

OBJECTIVE: To investigate whether the decrease in dyspnea in neuromuscular diseases after air stacking (AS) occurs mostly in patients with decreased inspiratory muscle force and ensuing chest wall restriction or heterogeneous ventilation across the lungs. DESIGN: Interventional, before-after study. SETTING: A neurorehabilitation inpatient and outpatient center. PARTICIPANTS: Fifteen consecutive adult patients affected by neuromuscular diseases (N=15). INTERVENTIONS: AS treatment. MAIN OUTCOME MEASURES: Patients had vital capacity (VC) and sniff nasal inspiratory pressure (SNIP) measured. We measured Borg score, oxygen saturation, and ventilation heterogeneity across the lung as estimated from the difference between respiratory resistance at 5 and 19 Hz (R5-19) with the forced oscillation technique before and 5, 30, 60, and 120 minutes after applying AS. RESULTS: Before AS, Borg score was significantly related to R5-19 (r2 0.46, P<.05) but not to VC % predicted, SNIP % predicted, and time since symptom onset. After AS, average Borg score gradually decreased (P=.005), whereas inspiratory flow resistance at 5 Hz, R5-19, and inspiratory reactance at 5 Hz tended to improve, despite not reaching statistical significance. The decrease in dyspnea at 60 and 120 minutes after AS significantly correlated with baseline R5-19 (r2 0.49, P<.01 and r2 0.29, P<.05, respectively), but not with VC % predicted, SNIP % predicted, time since symptom onset, and clinical severity score for patients affected by amyotrophic lateral sclerosis. CONCLUSIONS: These findings suggest that dyspnea in neuromuscular diseases is related to heterogeneous ventilation rather than inspiratory muscle force and/or lung volumes decrease. Restoring ventilation distribution across the lungs with AS appears to improve dyspnea.

Autotitrating external positive end-expiratory airway pressure to abolish expiratory flow limitation during tidal breathing in patients with severe COPD: a physiological study.

BACKGROUND: The optimal noninvasive application of external positive end-expiratory pressure (EPAP) to abolish tidal-breathing expiratory flow limitation (EFLT) and minimise intrinsic positive end-expiratory pressure (PEEPi) is challenging in COPD patients. We investigated whether auto-titrating EPAP, using the forced oscillation technique (FOT) to detect and abolish EFLT, would minimise PEEPi, work of breathing and neural respiratory drive (NRD) in patients with severe COPD. METHODS: Patients with COPD with chronic respiratory failure underwent auto-titration of EPAP using a FOT-based algorithm that detected EFLT. Once optimal EPAP was identified, manual titration was performed to assess NRD (using diaphragm and parasternal intercostal muscle electromyography, EMGdi and EMGpara, respectively), transdiaphragmatic inspiratory pressure swings (ΔP di), transdiaphragmatic pressure-time product (PTPdi) and PEEPi, between EPAP levels 2 cmH2O below to 3 cmH2O above optimal EPAP. RESULTS: Of 10 patients enrolled (age 65±6 years; male 60%; body mass index 27.6±7.2 kg.m-2; forced expiratory volume in 1 s 28.4±8.3% predicted), eight had EFLT, and optimal EPAP was 9 (range 4-13) cmH2O. NRD was reduced from baseline EPAP at 1 cmH2O below optimal EPAP on EMGdi and at optimal EPAP on EMGpara. In addition, at optimal EPAP, PEEPi (0.80±1.27 cmH2O versus 1.95± 1.70 cmH2O; p<0.05) was reduced compared with baseline. PTPdi (10.3±7.8 cmH2O·s-1 versus 16.8±8.8 cmH2O·s-1; p<0.05) and ΔP di (12.4±7.8 cmH2O versus 18.2±5.1 cmH2O; p<0.05) were reduced at optimal EPAP+1 cmH2O compared with baseline. CONCLUSION: Autotitration of EPAP, using a FOT-based algorithm to abolish EFLT, minimises transdiaphragmatic pressure swings and NRD in patients with COPD and chronic respiratory failure.

Telemonitoring in Chronic Obstructive Pulmonary Disease (CHROMED). A Randomized Clinical Trial.

RATIONALE: Early detection of chronic obstructive pulmonary disease (COPD) exacerbations using telemonitoring of physiological variables might reduce the frequency of hospitalization. OBJECTIVES: To evaluate the efficacy of home monitoring of lung mechanics by the forced oscillation technique and cardiac parameters in older patients with COPD and comorbidities. METHODS: This multicenter, randomized clinical trial recruited 312 patients with Global Initiative for Chronic Obstructive Lung Disease grades II to IV COPD (median age, 71 yr [interquartile range, 66-76 yr]; 49.6% grade II, 50.4% grades III-IV), with a history of exacerbation in the previous year and at least one nonpulmonary comorbidity. Patients were randomized to usual care (n = 158) or telemonitoring (n = 154) and followed for 9 months. All telemonitoring patients self-assessed lung mechanics daily, and in a subgroup with congestive heart failure (n = 37) cardiac parameters were also monitored. An algorithm identified deterioration, triggering a telephone contact to determine appropriate interventions. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were time to first hospitalization (TTFH) and change in the EuroQoL EQ-5D utility index score. Secondary outcomes included: rate of antibiotic/corticosteroid prescription; hospitalization; the COPD Assessment Tool, Patient Health Questionnaire-9, and Minnesota Living with Heart Failure questionnaire scores; quality-adjusted life years; and healthcare costs. Telemonitoring did not affect TTFH, EQ-5D utility index score, antibiotic prescriptions, hospitalization rate, or questionnaire scores. In an exploratory analysis, telemedicine was associated with fewer repeat hospitalizations (-54%; P = 0.017). CONCLUSIONS: In older patients with COPD and comorbidities, remote monitoring of lung function by forced oscillation technique and cardiac parameters did not change TTFH and EQ-5D. Clinical trial registered with www.clinicaltrials.gov (NCT 01960907).

Within-breath oscillometry for identifying exercise-induced bronchoconstriction in pediatric patients reporting symptoms with exercise.

Background: Evaluating oscillometry parameters separately for the inspiratory and expiratory breath phases and their within-breath differences can help to identify exercise-induced bronchoconstriction (EIB) in pediatric outpatients disclosing exercise-induced symptoms (EIS). Aims: To assess the response in impedance parameters following an exercise challenge in patients reporting EIS. Methods: Sixty-eight patients reporting EIS (34 asthmatics and 34 suspected of asthma, age mean = 10.8 years, range = 6.0-16.0) underwent an incremental treadmill exercise test. Spirometry was performed at baseline and 1, 5-, 10-, 15-, and 20-min post exercise. Oscillometry was performed at baseline and at 3- and 18-min post exercise. Bronchodilator response to 200 µg albuterol was then assessed. EIB was defined as a forced expiratory volume in 1 s (FEV1) fall ≥10% from baseline. Expiratory and inspiratory resistance (Rrs) and reactance (Xrs), their z-score (Ducharme et al. 2022), and their mean within-breath differences (ΔRrs = Rrsexp-Rrsinsp, ΔXrs = Xrsexp-Xrsinsp) were calculated. Receiver operating characteristic (ROC) curves and their areas (AUCs) were used to evaluate impedance parameters' performances in classifying EIB. Results: Asthmatic patients developed EIB more frequently than those suspected of asthma [18/34 (52.9%) vs. 2/34 (5.9%), p < 0.001]. In the 20 subjects with EIB, Rrsinsp, Rrsexp, Xrsinsp, and Xrsexp peaked early (3'), and remained steady except for Xrsinsp, which recovered faster afterward. ΔXrs widened 18 min following the exercise and reversed sharply after bronchodilation (BD) (-1.81 ± 1.60 vs. -0.52 ± 0.80 cmH2O × s/L, p < 0.001). Cutoffs for EIB leading to the highest AUCs were a rise of 0.41 in z-score Rrsinsp (Se: 90.0%, Sp: 66.7%), and a fall of -0.64 in z-score Xrsinsp (Se: 90.0%, Sp: 75.0%). Accepting as having "positive" postexercise oscillometry changes those subjects who had both z-scores beyond respective cutoffs, sensitivity for EIB was 90.0% (18/20) and specificity, 83.3% (40/48). Conclusion: Oscillometry parameters and their within-breath differences changed markedly in pediatric patients presenting EIB and were restored after the bronchodilator. Strong agreement between z-scores of inspiratory oscillometry parameters and spirometry supports their clinical utility, though larger studies are required to validate these findings in a broader population.

Optimizing positive end-expiratory pressure by oscillatory mechanics minimizes tidal recruitment and distension: an experimental study in a lavage model of lung injury.

INTRODUCTION: It is well established that during mechanical ventilation of patients with acute respiratory distress syndrome cyclic recruitment/derecruitment and overdistension are potentially injurious for lung tissues. We evaluated whether the forced oscillation technique (FOT) could be used to guide the ventilator settings in order to minimize cyclic lung recruitment/derecruitment and cyclic mechanical stress in an experimental model of acute lung injury. METHODS: We studied six pigs in which lung injury was induced by bronchoalveolar lavage. The animals were ventilated with a tidal volume of 6 ml/kg. Forced oscillations at 5 Hz were superimposed on the ventilation waveform. Pressure and flow were measured at the tip and at the inlet of the endotracheal tube respectively. Respiratory system reactance (Xrs) was computed from the pressure and flow signals and expressed in terms of oscillatory elastance (EX5). Positive end-expiratory pressure (PEEP) was increased from 0 to 24 cm H2O in steps of 4 cm H2O and subsequently decreased from 24 to 0 in steps of 2 cm H2O. At each PEEP step CT scans and EX5 were assessed at end-expiration and end-inspiration. RESULTS: During deflation the relationship between both end-expiratory and end-inspiratory EX5 and PEEP was a U-shaped curve with minimum values at PEEP = 13.4 ± 1.0 cm H2O (mean ± SD) and 13.0 ± 1.0 cm H2O respectively. EX5 was always higher at end-inspiration than at end-expiration, the difference between the average curves being minimal at 12 cm H2O. At this PEEP level, CT did not show any substantial sign of intra-tidal recruitment/derecruitment or expiratory lung collapse. CONCLUSIONS: Using FOT it was possible to measure EX5 both at end-expiration and at end-inspiration. The optimal PEEP strategy based on end-expiratory EX5 minimized intra-tidal recruitment/derecruitment as assessed by CT, and the concurrent attenuation of intra-tidal variations of EX5 suggests that it may also minimize tidal mechanical stress.

A portable fan-based device for evaluating lung function in horses by the forced oscillation technique.

Objective. The assessment of lung mechanics in horses is nowadays based on invasive methods that may require sedation. The forced oscillation technique (FOT) allows the non-invasive assessment of respiratory mechanics during spontaneous breathing, but current devices are complex, cumbersome, expensive, and difficult to be applied in horses.Approach. We developed a portable FOT device based on a novel approach in which the pressure waveforms are generated by a servo-controlled ducted fan. This new approach allows the design of devices that are more sturdy, compact, and portable compared to already existing approaches. The prototype includes 1) a small microcontroller-based electronic board for controlling the fan and measuring flow and pressure and 2) an optimized data processing algorithm.Main results. This device provides a maximum error of 0.06 cmH2O·s/L and 0.15 cmH2O·s/L in measuring respiratory resistance and reactance duringin-vitrovalidation. A pilot study was also performed on three healthy horses and three horses with severe equine asthma (SEA) and it demonstrated good tolerability and feasibility of the new device. Total respiratory system resistance (Rrs) and reactance (Xrs) significantly differed (p< 0.05) between groups. At 5 Hz,Rrswas 0.66 ± 0.02 cmH2O·s/L and 0.94 ± 0.07 cmH2O·s/L in healthy and in SEA, respectively.Xrs0.38 ± 0.02 cmH2O·s/L and -0.27 ± 0.05 cmH2O·s/L.Significance. This novel approach for applying FOT allowed the development of a small, affordable, and portable device for the non-invasive evaluation of respiratory mechanics in spontaneously breathing horses, providing a useful new tool for improving veterinary respiratory medicine. Moreover, our results provide supporting evidence of the value of this novel approach for developing portable FOT devices also for applications in humans.

Positive end-expiratory pressure optimization with forced oscillation technique reduces ventilator induced lung injury: a controlled experimental study in pigs with saline lavage lung injury.

INTRODUCTION: Protocols using high levels of positive end-expiratory pressure (PEEP) in combination with low tidal volumes have been shown to reduce mortality in patients with severe acute respiratory distress syndrome (ARDS). However, the optimal method for setting PEEP is yet to be defined. It has been shown that respiratory system reactance (Xrs), measured by the forced oscillation technique (FOT) at 5 Hz, may be used to identify the minimal PEEP level required to maintain lung recruitment. The aim of the present study was to evaluate if using Xrs for setting PEEP would improve lung mechanics and reduce lung injury compared to an oxygenation-based approach. METHODS: 17 pigs, in which acute lung injury (ALI) was induced by saline lavage, were studied. Animals were randomized into two groups: in the first PEEP was titrated according to Xrs (FOT group), in the control group PEEP was set according to the ARDSNet protocol (ARDSNet group). The duration of the trial was 12 hours. In both groups recruitment maneuvers (RM) were performed every 2 hours, increasing PEEP to 20 cmH2O. In the FOT group PEEP was titrated by monitoring Xrs while PEEP was reduced from 20 cmH2O in steps of 2 cmH2O. PEEP was considered optimal at the step before which Xrs started to decrease. Ventilatory parameters, lung mechanics, blood gases and hemodynamic parameters were recorded hourly. Lung injury was evaluated by histopathological analysis. RESULTS: The PEEP levels set in the FOT group were significantly higher compared to those set in the ARDSNet group during the whole trial. These higher values of PEEP resulted in improved lung mechanics, reduced driving pressure, improved oxygenation, with a trend for higher PaCO2 and lower systemic and pulmonary pressure. After 12 hours of ventilation, histopathological analysis showed a significantly lower score of lung injury in the FOT group compared to the ARDSNet group. CONCLUSIONS: In a lavage model of lung injury a PEEP optimization strategy based on maximizing Xrs attenuated the signs of ventilator induced lung injury. The respiratory system reactance measured by FOT could thus be an important component in a strategy for delivering protective ventilation to patients with ARDS/acute lung injury.

Artificial intelligence for quality control of oscillometry measures.

BACKGROUND: The forced oscillation technique (FOT) allows non-invasive lung function testing during quiet breathing even without expert guidance. However, it still relies on an operator for excluding breaths with artefacts such as swallowing, glottis closure and coughing. This manual selection is operator-dependent and time-consuming. We evaluated supervised machine learning methods to exclude breaths with artefacts from data analysis automatically. METHODS: We collected 932 FOT measurements (Resmon Pro Full, Restech) from 155 patients (6-87 years) following the European Respiratory Society (ERS) technical standards. Patients were randomly assigned to either a training (70%) or test set. For each breath, we computed 71 features (including anthropometric, pressure stimulus, breathing pattern, and oscillometry data). Univariate filter, multivariate filter and wrapper methods for feature selection combined with several classification models were considered. RESULTS: Trained operators identified 4333 breaths with- and 10244 without artefacts. Features selection performed by a wrapper method combined with an AdaBoost tree model provided the best performance metrics on the test set: Balanced Accuracy = 85%; Sensitivity = 79%; Specificity = 91%; AUC-ROC = 0.93. Differences in FOT parameters computed after manual or automatic breath selection was less than ∼0.25 cmH2O*s/L for 95% of cases. CONCLUSION: Supervised machine-learning techniques allow reliable artefact detection in FOT diagnostic tests. Automating this process is fundamental for enabling FOT for home monitoring, telemedicine, and point-of-care diagnostic applications and opens new scenarios for respiratory and community medicine.

Effect of stimulating waveform and of data processing on respiratory impedance measurement.

OBJECTIVE: Several commercial and custom-made forced oscillation technique (FOT) devices are used to assess respiratory system impedance. The impulse oscillometry system (IOS) is a widespread device, which yields similar but not identical results to those provided by other FOT systems. Differences may be related to the forcing waveform, the device hardware, or the data processing algorithms. We evaluated the agreement between resistance (R rs) and reactance (X rs) measurements while alternating between different forcing waveforms and data processing algorithms. APPROACH: We performed pre- and post-bronchodilator measurements in 20 patients with respiratory complaints. We generated pulse waveforms using an IOS, and sinusoidal oscillations by replacing the IOS loudspeaker with customized loudspeaker providing a 5 Hz sinusoidal pressure signal. Pressure and flow were measured using the IOS sensors and breathing circuit. We developed a data processing algorithm compatible to both forcing signals. We also applied commercial IOS software during pulse waveform and a least mean square (lms) algorithm during sinusoidal waveform. MAIN RESULTS: The median (5th, 95th percentile) differences between R rs and X rs were (1) -0.35 (-2.49, 1.23) and 0.16 (-1.63, 3.07 cmH2O*s l-1, when the same algorithm was used during pulse vs sinusoidal stimulus; (2) 0.34 (-2.33, 5.98) and 0.57 (-2.64, 6.09) cmH2O*s l-1, when our algorithm and the IOS software were used during pulse waveform; and (3) 0.33 (-1.20, 6.05) and 0.25 (-4.94, 4.28) cmH2O*s l-1 when the IOS software was used during pulse and the lms algorithm during sinusoidal waveforms. SIGNIFICANCE: Both forcing signal and data processing contribute to differences in impedance values measured by different FOT devices.

Airway hyperresponsiveness with chest strapping: A matter of heterogeneity or reduced lung volume?

Chest wall strapping has been recently shown to be associated with an increase in airway responsiveness to methacholine. To investigate whether this is the result of the decreased lung volume or an increased heterogeneity due to chest wall distortion, ten healthy volunteers underwent a methacholine challenge at control conditions and after selective strapping of the rib cage, the abdomen or the whole chest wall resulting in similar decrements of functional residual capacity and total lung capacity but causing different distribution of the bronchoconstrictor. Methacholine during strapping reduced forced expiratory flow, dynamic compliance, and reactance at 5Hz and increased pulmonary resistance and respiratory resistance at 5Hz that were significantly greater than at control and associated with a blunted bronchodilator effect of the deep breath. However, no significant differences were observed between selective and total chest wall strapping, suggesting that the major mechanism for increasing airway responsiveness with chest wall strapping is the breathing at low lung volume rather than regional heterogeneities.

Short-term variability in respiratory impedance and effect of deep breath in asthmatic and healthy subjects with airway smooth muscle activation and unloading.

Inspiratory resistance (RINSP) and reactance (XINSP) were measured for 7 min at 5 Hz in 10 subjects with mild asymptomatic asthma and 9 healthy subjects to assess the effects of airway smooth muscle (ASM) activation by methacholine (MCh) and unloading by chest wall strapping (CWS) on the variability of lung function and the effects of deep inspiration (DI). Subjects were studied at control conditions, after MCh, with CWS, and after MCh with CWS. In all experimental conditions XINSP was significantly more negative in subjects with asthma than in healthy subjects, suggesting greater inhomogeneity in the former. However, the variability in both RINSP and XINSP was increased by either ASM activation or CWS, without significant difference between groups. DI significantly reversed MCh-induced changes in RINSP both in subjects with asthma and healthy subjects, but XINSP in the former only. This effect was impaired by CWS more in subjects with asthma than in healthy subjects. The velocity of RINSP and XINSP recovery after DI was faster in subjects with asthma than healthy subjects. In conclusion, these results support the opinion that the short-term variability in respiratory impedance is related to ASM tone or operating length, rather than to the disease. Nevertheless, ASM in individuals with asthma differs from that in healthy individuals in an increased velocity of shortening and a reduced sensitivity to mechanical stress when strain is reduced.

Airway distensibility with lung inflation after allogeneic haematopoietic stem-cell transplantation.

The ability to reverse induced-bronchoconstriction by deep-inhalation increases after allogeneic haematopoietic stem-cell transplantation (HSCT), despite a decreased total lung capacity (TLC). We hypothesized that this effect may be due to an increased airway distensibility with lung inflation, likely related to an increment in lung stiffness. We studied 28 subjects, 2 weeks before and 2 months after HSCT. Within-breath respiratory system conductance (G(rs)) at 5, 11 and 19 Hz was measured by forced oscillation technique (FOT) at functional residual capacity (FRC) and TLC. Changes in conductance at 5Hz (G(rs5)) were related to changes in lung volume (ΔG(rs5)/ΔV(L)) to estimate airway distensibility. G(rs) at FRC showed a slight but significant increase at all forcing frequencies by approximately 12-16%. TLC decreased after HSCT whereas the ΔG(rs5)/ΔV(L) ratio became higher after than before HSCT and was positively correlated (R2=0.87) with lung tissue density determined by quantitative CT scanning. We conclude that airway caliber and distensibility with lung inflation are increased after HSCT. This effect seems to be related to an increase in lung stiffness and must be taken into account when interpreting lung function changes after HSCT.

Optimisation of positive end-expiratory pressure by forced oscillation technique in a lavage model of acute lung injury.

PURPOSE: We evaluated whether oscillatory compliance (C(X5)) measured by forced oscillation technique (FOT) at 5 Hz may be useful for positive end-expiratory pressure (PEEP) optimisation. METHODS: We studied seven pigs in which lung injury was induced by broncho-alveolar lavage. The animals were ventilated in volume control mode with a tidal volume of 6 ml/kg. Forced oscillations were superimposed on the ventilation waveform for the assessment of respiratory mechanics. PEEP was increased from 0 to 24 cmH(2)O in steps of 4 cmH(2)O and subsequently decreased from 24 to 0 in steps of 2 cmH(2)O. At each 8-min step, a CT scan was acquired during an end-expiratory hold, and blood gas analysis was performed. C(X5) was monitored continuously, and data relative to the expiratory hold were selected and averaged for comparison with CT and oxygenation. RESULTS: Open lung PEEP (PEEP(ol)) was defined as the level of PEEP corresponding to the maximum value of C(X5) on the decremental limb of the PEEP trial. PEEP(ol) was on average 13.4 (± 1.0) cmH(2)O. For higher levels of PEEP, there were no significant changes in the amount of non-aerated tissue (V(tissNA)%). In contrast, when PEEP was reduced below PEEP(ol), V(tissNA)% dramatically increased. PEEP(ol) was able to prevent a 5% drop in V(tissNA)% with 100% sensitivity and 92% specificity. At PEEP(ol) V(tissNA)% was significantly lower than at the corresponding PEEP level on the incremental limb. CONCLUSIONS: The assessment of C(X5) allowed the definition of PEEP(ol) to be in agreement with CT data. Thus, FOT measurements of C(X5) may provide a non-invasive bedside tool for PEEP titration.

Comparison of a visual analogue scale and Lake Louise symptom scores for acute mountain sickness.

Assessment of the presence and severity of acute mountain sickness (AMS) is based on subjective reporting of the sensation of symptoms. The Lake Louise symptom scoring system (LLS) uses categorical variables to rate the intensity of AMS-related symptoms (headache, gastrointestinal distress, dizziness, fatigue, sleep quality) on 4-point ordinal scales; the sum of the answers is the LLS self-score (range 0-15). Recent publications indicate a potential for a visual analogue scale (VAS) to quantify AMS. We tested the hypothesis that overall and single-item VAS and LLS scores scale linearly. We asked 14 unacclimatized male subjects [age 41 (14), mean (SD) yr; height 176 (3) cm; weight 75 (9) kg] who spent 2 days at 3647 m and 4 days at 4560 m to fill out LLS questionnaires, with a VAS for each item (i) and a VAS for the overall (o) sensation of AMS, twice a day (n = 172). Even though correlated (r = 0.84), the relationship between LLS(o) and VAS(o) was distorted, showing a threshold effect for LLS(o) scores below 5, with most VAS(o) scores on one side of the identity line. Similar threshold effects were seen for the LLS(i) and VAS(i) scores. These findings indicate nonlinear scaling characteristics that render difficult a direct comparison of studies done with either VAS or LLS alone.

Airway distensibility and volume recruitment with lung inflation in COPD.

The effects of full lung inflation on respiratory conductance (Grs) and reactance (Xrs) were measured in 15 subjects with moderate to severe chronic obstructive pulmonary disease (COPD) and 11 matched healthy control subjects. Airway distensibility was estimated from the ratio of the difference of Grs between functional residual capacity and total lung capacity to the relevant changes in lung volume (ΔGrs/ΔVl) or transpulmonary pressure (ΔGrs/ΔPtp). Similar analysis was applied to Xrs to estimate lung volume recruitment (ΔXrs/ΔVl or ΔXrs/ΔPtp). The extent of emphysema in COPD subjects was estimated from the percentage of low attenuation area (LAA) at high-resolution computed tomography. At baseline, ΔGrs/ΔVl and ΔXrs/ΔVl were significantly less in COPD than control subjects, indicating less distensibility and volume recruitment in the former. In COPD, ΔGrs/ΔPtp and ΔXrs/ΔPtp were uncorrelated with LAA but correlated with 1-s forced expiratory volume and with each other. After albuterol, both ΔGrs/ΔPtp and ΔGrs/ΔVl became significantly and negatively correlated with LAA, while ΔXrs/ΔPtp and ΔXrs/ΔVl decreased significantly independently of LAA. Moreover, ΔGrs/ΔPtp and ΔXrs/ΔPtp with lung inflation were no longer correlated with each other, suggesting that airway distensibility and volume recruitment were affected differently by airway smooth muscle tone. Assuming that Grs mainly reflects airway caliber and Xrs the number of ventilated lung units, we conclude that airway smooth muscle contributes to airway stiffness and ventilation inhomogeneities in COPD subjects with prevailing bronchitis but only to the latter in those with more emphysema. We suggest that changes of airway distensibility and volume recruitment with a bronchodilator may be useful for disease phenotyping.