Peripheral Airways Research Articles

Oscillometry – The future of estimating pulmonary functions

The prevalence of asthma is increasing rapidly, worldwide, due to changing gene-environment interactions. The rate of rise is more in resource poor nations due to lack of knowledge and non-availability of expertise. Monitoring of lung functions is mandatory for diagnosis and further management of asthmatic patients. Spirometry, the widely available investigation, is the gold standard test used for mapping pulmonary dynamicity. It has got its own limitations in the form of operational difficulties in children, the elderly, and in those with neuromuscular or behavioral issues. In the current era of COVID-19 pandemic, the utility of spirometry has been further restricted to selected cohort only, due to potential risk of viral transmission during the procedure. Oscillometry technique has been used previously, to monitor lung functions, with promising results. Ultrasonic waves of various frequencies accompany the tidal breath of patients and respiratory impedance is calculated by measured pressure and flow signals from exhaled breath. The results are interpreted in the form of resistance, reactance, resonant frequency, and reactance area. Various manufacturers have developed different mechanical models with slight variation in impulse pattern till date. There are certain distinct advantages of oscillometry over spirometry. Being tidal breath-based maneuver, it is more child friendly. People with neuromuscular weakness, cognitive limitations, and the elderly can easily perform it with only minor understanding and effort. Oscillometry is more sensitive than spirometry in detecting peripheral airway diseases. Post-bronchodilator reversibility can be evaluated by comparing with the baseline respiratory characteristics. Their utility in restrictive diseases and vocal cord dysfunction has also been explored. Less aerosol generation during the normal tidal breath is another advantage of oscillometry, over spirometry needing forceful efforts, which makes it more suitable for use in viral pandemic situations for monitoring patients with both asthma and pneumonia. More research is needed, in various geographic locations and heterogeneous populations, to devise the normative data of oscillometric parameters. Simultaneously, there is an urgent need for standardization of available machines at global platform.

Small-airway dysfunction in paediatric asthma.

Asthma is a chronic inflammatory airway disorder that can involve the entire bronchial tree. Increasing evidence shows that ventilation heterogeneity and small airway dysfunction are relevant factors in the pathogenesis of asthma and represent a hallmark in adults with persistent asthma. Little is known about the contribution of peripheral airway impairment in paediatric asthma, mainly due to the inaccessibility to evaluation by noninvasive techniques, which have only been widely available in recent years. Emerging evidence suggests that small airways are affected from the early stages of the disease in childhood-onset asthma. Conventional lung function measurement, using spirometry, is unable to sensitively evaluate small airway function and may become abnormal only once there is a significant burden of disease. Recent studies suggest that chronic inflammation and dysfunction in the small airways, as detected with new advanced techniques, are risk factors for asthma persistence, asthma severity, worse asthma control and loss of pulmonary function with age, both in adults and children. Knowing the extent of central and peripheral airway involvement is clinically relevant to achieve asthma control, reduce bronchial hyper-responsiveness and monitor response to asthma treatment. This review outlines the recent evidence on the role of small airway dysfunction in paediatric asthma development and control, and addresses how the use of new diagnostic techniques available in outpatient clinical settings, namely impulse oscillometry and multiple breath washout, could help in the early detection of small airway impairment in children with preschool wheezing and school-age asthma and potentially guide asthma treatment.

Consistent Pulmonary Drug Delivery with Whole Lung Deposition Using the Aerosphere Inhaler: A Review of the Evidence.

Metered dose inhalers (MDIs) are one of the most common device types for delivering inhaled therapies. However, there are several technical challenges in development and drug delivery of these medications. In particular, suspension-based MDIs are susceptible to suspension heterogeneity, in vitro drug–drug interactions, and patient handling errors, which may all affect drug delivery. To overcome these challenges, new formulation approaches are required. The AerosphereTM inhaler, formulated using co-suspension delivery technology, combines drug crystals with porous phospholipid particles to create stable, homogenous suspensions that dissolve once they reach the airways. Two combination therapies using this technology have been developed for the treatment of COPD: glycopyrrolate/formoterol fumarate (GFF MDI; dual combination) and budesonide/glycopyrrolate/formoterol fumarate (BGF MDI; triple combination). Here, we review the evidence with a focus on studies assessing dose delivery, lung deposition, and effects on airway geometry. In vitro assessments have demonstrated that the Aerosphere inhaler provides consistent dose delivery, even in the presence of simulated patient handling errors. Combination therapies delivered with this technology also show a consistent fine particle fraction (FPF) and an optimal particle size distribution for delivery to the central and peripheral airways even when multiple drugs are delivered via the same inhaler. Studies using gamma scintigraphy and functional respiratory imaging have demonstrated that GFF MDI is effectively deposited in the central and peripheral airways, and provides clinically meaningful benefits on airway volume and resistance throughout the lung. Overall, studies suggest that the Aerosphere inhaler, formulated using co-suspension delivery technology, may offer advantages over traditional formulations, including consistent delivery of multiple components across patient handling conditions, optimal particle size and FPF, and effective delivery to the central and peripheral airways. Future studies may provide additional evidence to further characterize the clinical benefits of these technical improvements in MDI drug delivery.

The Impact of beta blockade on the cardio-respiratory system and symptoms during exercise.

BackgroundBeta blockers prolong life in patients with cardiovascular diseases. Negative chronotropic and inotropic effects carry the potential to adversely effect peripheral skeletal and airway smooth muscle contributing to further fatigue, dyspnea and exercise intolerance.Research questionsDo beta-blockers reduce maximal power output (MPO), VO2 max, cardiorespiratory responses, increase the perceived effort required to cycle and breath during cardiopulmonary exercise tests (CPET) and limit the capacity to exercise?MethodsRetrospective observational study of subjects performing CPET to capacity from 1988 to 2012. Subjects with and without beta-blockers were compared: baseline physiological characteristics, MPO, VO2 max, heart rate max, ventilation responses and perceived exertion required to cycle and breathe (modified Borg scale). Forward stepwise linear additive regression was performed with MPO as the dependent factor with height, age, gender, muscle strength, FEV1 and DLCO as independent contributors.Results42,771 subjects were included 7,787 were receiving beta-blocker [mean age 61 yrs, BMI 28.40 kg/m2, 9% airflow obstruction (FEV1/FVC<0.7)] and 34,984 were not [mean age 51yrs, BMI 27.40 kg/m2, 11% airflow obstruction]. Heart rate was lower by 18.2% (95% C.I. 18.15–18.38) (p<0.0001) while Oxygen pulse (VO2/HR) was higher by 19.5% (95% C.I. 19.3–19.7) in those receiving beta blockers. Maximum power output (MPO) was 3.3% lower in those taking beta-blockers. The perceived effort required to cycle and breathe (mBorg) was 8% lower in those taking beta-blockers.InterpretationIncreases in oxygen pulse minimize the reduction in exercise intolerance and symptom handicap associated with beta-blockers.

Peripheral obstruction without airflow limitation is rare and not specific to asthma in children.

Peripheral (or small) airway obstruction (PAO) is considered a marker of childhood asthma but the techniques able to directly measure it are rarely used in routine. Usual spirometry and plethysmography can detect a certain degree of PAO when reduced forced vital capacity (FVC) is associated to normal forced expiratory volume in 1 s (FEV1 ) to FVC ratio, and normal total lung capacity (TLC). The frequency of this functional pattern has never been studied in different pediatric respiratory conditions. To assess the prevalence and outcome of PAO in children with different diseases or symptoms, we retrospectively extracted from our database all files of Caucasian subjects encompassing spirometry and plethysmography measurements. Spirometry patterns (normal, airflow limitation [AFL; low FEV1 /FVC], low FVC [with normal FEV1 /FVC]) and final functional patterns (normal, AFL, PAO, restrictive [low TLC], or mixed) were described. We included 4394 files recorded in 1794 children (median [IQR] age: 10.7 [9.2-12.9] years). At inclusion, 125 (7%) children had low FVC of which 56 (44.8%, and 3.1% [95% CI 2.3-3.9] of the whole population) had PAO. PAO prevalence increased with age (OR (95% CI) per 2-year-increase: 2.26 (1.59-3.23); p < .001), and was more frequent in chronic bronchial diseases other than asthma (1.6% vs. 8.0%). On repeated tests, PAO frequently normalized (26.1%) or persisted (43.5%), but it less often progressed into AFL (13%) or restrictive (13%) patterns. PAO is an infrequent nonspecific and persistent functional pattern. Its prevalence increases with age and in diagnosis of chronic respiratory diseases other than asthma.

Forced expiratory flow during 25%-75% of expiration in middle aged obese and non-obese females – A comparitive study

Introduction: Obesity can cause various health hazards in women in many ways. Overweight or being obese is associated with various risk factors like diabetes and coronary artery disease in women. The incidence of obesity is increasing worldwide. Obesity can cause alteration in pulmonary function which may lead to early morbidity and mortality. FEF 25%-75% is one of the most effort independent portion of the curve, more sensitive parameter to airflow in peripheral airways, where disease of chronic airflow obstruction can begin. Reduced Expiratory Flow rate value in obese individuals may be probably due to increase in the total peripheral resistance and airway resistance with obesity. Hence the present study was undertaken to know the impact of obesity on Forced Expiratory Flow rate25%-75% in middle aged obese females. Aims and Objectives: The present study was conducted ` to compare Pulmonary function test parameter FEF 25%-75% in middle aged obese and non-obese females, to determine the impact of obesity on FEF25%-75%. Materials and Methods: Dynamic Pulmonary Function tests (PFTs) of 50 normal, healthy, non-obese middle aged females and 50 healthy but obese middle aged females, age group 30-45 years of Hubli city were determined and were compared with its normal counterparts. Study subjects were classified into obese and non-obese based on WHO classification of BMI. To obtain the dynamic pulmonary function test computerized Spirometer Eazy on-PC model were used. Dynamic PFT parameter FEF25%-75%was used as measure of lung function. Results: In our Study conducted, middle aged obese females had FEF25%-75% (litre) of 2.53± 0.85 compared to corresponding values in controls were 2.77±1.06.Our study showed statistically significant differences between two groups. Conclusion: In our study Dynamic pulmonary function test parameter FEF25%-75% showed statistically significant reduction in obese compared to non-obese middle aged females. Keywords: Obesity, Middle aged obese

Mobile 3D Intraprocedural Fluoroscopy in Combination With Ultrathin Bronchoscopy for Biopsy of Peripheral Lung Nodules.

Despite development of multiple technologies, distinguishing benign from malignant lung nodules when they are still small in size is challenging. A high yield and minimally invasive bronchoscopic technology with low cost for diagnosis of small lung lesions is needed in pulmonary and lung cancer clinical practice. Peripheral airway bronchoscopy using thin and most recently ultrathin bronchoscopes improve visualization of small airways. The novel mobile 2D/3D C-Arm fluoroscopy system is a complementary tool along with radial endobronchial ultrasound in detecting small lung nodules with real-time high-quality multidimensional image confirmation during bronchoscopy. This combined technology can be easily acquired in any bronchoscopy room, and potentially affect lung nodule practice significantly.

Prevalence and features of IOS-defined small airway disease across asthma severities

BackgroundImpulse oscillometry (IOS) is a noninvasive method based on the forced oscillation technique able to detect small airway dysfunction (SAD) in asthma. We aimed to analyze the prevalence and the functional features of IOS-defined SAD across the different Global Initiative for Asthma (GINA) steps. MethodsA cross-sectional, single-center study in which 400 consecutive adult patients with physician-diagnosed, community-managed asthma underwent standard spirometry and IOS, and were stratified by stepwise GINA classification. SAD was defined by IOS as a fall in resistance from 5 to 20 Hz [R5–R20]>0.07kPa × s × L−1. ResultsThe prevalence of IOS-defined SAD ranged between 58.3% (GINA step 2) and 78.6% (GINA step 5), without statistically significant difference within GINA steps (p > 0.05 in all comparisons). Isolated SAD (i.e. without proximal airways involvement) was similarly represented across GINA steps 2–4. Peripheral airways resistance (R5-R20) tended to a progressive increase with the worsening of GINA steps, and was significantly higher in steps 4–5 compared to the other steps (p < 0.05).The proportion of patients with FEF25–75%-defined SAD (<60%) was lower than the IOS-defined one in GINA steps 2–4 (p < 0.05). Only non-significant or weak inverse correlations between R5-R20 and FEF25–75% were observed within each GINA step, with the exception of GINA step 5, which showed a strong, inverse correlation (r = −0.80, p = 0.0005). ConclusionsThis study shows that first, IOS-defined SAD is overwhelmingly present across asthma severities; second, airways resistance increases with the worsening of GINA steps; and third, SAD may be overlooked by standard spirometry, especially in milder asthma.

Multichannel lung sound analysis to detect severity of lung disease in cystic fibrosis

ObjectiveRespiratory disease in Cystic fibrosis (CF) patients is one of the main causes of the reduction in pulmonary function and death. The primary goals of CF treatment include maintaining or improving pulmonary function and reducing the rate of pulmonary function decline. Therefore, the severity of lung disease should be monitored in CF patients. The objective of this study is to examine multichannel lung sound analysis in detecting the severity of lung disease in CF patients. Methods209 multichannel lung sound samples were recorded from thirty seven CF patients using a thirty channel acquisition system. Then, expiration to inspiration lung sound power ratio features in different frequency bands (E/I F) were extracted from large airway, upper airway and peripheral airway channels. These features were compared between the groups with different severity levels of the lung disease using Support Vector Machine, Artificial Neural Network, Decision tree and Naïve Baysian classifiers by ‘leave-one-sample-out’ method. ResultsIt was shown that features of upper airways and peripheral airways were more effective in discriminating normal from mild (91.1%) and moderate from severe (92.8%) respiratory sound samples, respectively. The best result for discriminating between all groups of severity was related to neural network classifier which performs 89.05% average accuracy. Also, ‘leave-one-subject-out’ method confirmed the results. ConclusionThe proposed multichannel lung sound analysis method was successful in discriminating different severity levels of CF lung disease. Moreover, analysis of different lung region signals in consecutive levels of lung disease was consistent with regional damage of lung in CF.

Increasing Sphingolipid Synthesis Alleviates Airway Hyperreactivity

Impaired sphingolipid synthesis is linked genetically to childhood asthma and functionally to airway hyperreactivity (AHR). The objective was to investigate whether sphingolipid synthesis could be a target for asthma therapeutics. The effects of GlyH-101 and fenretinide via modulation of de novo sphingolipid synthesis on AHR was evaluated in mice deficient in SPT (serine palmitoyl-CoA transferase), the rate-limiting enzyme of sphingolipid synthesis. The drugs were also used directly in human airway smooth-muscle and epithelial cells to evaluate changes in de novo sphingolipid metabolites and calcium release. GlyH-101 and fenretinide increased sphinganine and dihydroceramides (de novo sphingolipid metabolites) in lung epithelial and airway smooth-muscle cells, decreased the intracellular calcium concentration in airway smooth-muscle cells, and decreased agonist-induced contraction in proximal and peripheral airways. GlyH-101 also decreased AHR in SPT-deficient mice in vivo. This study identifies the manipulation of sphingolipid synthesis as a novel metabolic therapeutic strategy to alleviate AHR.

The Nature of Recruitment and De-Recruitment and Its Implications for Management of ARDS.

Recruitment maneuvers in ARDS are used to improve oxygenation and lung mechanics by applying high airway pressures to reopen collapsed or obstructed peripheral airways and alveoli. In the early 1990s, recruitment maneuvers became a central feature of a variant form of lung-protective ventilation known as open-lung ventilation. This strategy is based on the belief that repetitive opening and closing of distal airspaces induces shear injury and therefore contributes both to ventilator-induced lung injury and ARDS-associated mortality. However, the largest multi-center randomized controlled trial of open-lung ventilation in moderate to severe ARDS reported that recruitment maneuver plateau pressures of 50-60 cm H2O were associated with significantly higher mortality compared to traditional lung-protective ventilation. Despite being based on well conducted preclinical and clinical recruitment maneuver studies, the higher mortality associated with the open-lung ventilation strategy requires re-examining the assumptions and conclusions drawn from those previous studies. This narrative review examines the evidence used to design recruitment maneuver strategies. We also review the radiologic, rheologic, and histopathologic evidence regarding the nature of lung injury and the phenomena of recruitment and de-recruitment as it informs our perceptions of recruitment potential in ARDS. Major lung-protective ventilation clinical trial data and other clinical data are also examined to assess the practical necessity of recruitment maneuvers in ARDS and whether a subset of cases might benefit from pursuing recruitment maneuver therapy. Finally, a less a radical approach to recruitment maneuvers is offered that might achieve the goals of recruitment maneuvers with less risk of harm.

Methacholine-Induced Cough in the Absence of Asthma: Insights From Impulse Oscillometry.

IntroductionThe pathophysiologic differences between methacholine-induced cough but normal airway sensitivity (COUGH) and healthy individuals (CONTROL) are incompletely understood and may be due to differences in the bronchodilating effect of deep inspirations (DIs). The purpose of this study is to compare the bronchodilating effect of DIs in individuals with classic asthma (CA), cough variant asthma (CVA), and COUGH with CONTROL and to assess impulse oscillometry (IOS) measures as predictors of the bronchodilating effect of DIs.MethodsA total of 43 adults [18 female; 44.8 ± 12.3 years (mean ± SD); n = 11 CA, n = 10 CVA, n = 7 COUGH, n = 15 CONTROL] underwent modified high-dose methacholine challenge, with IOS and partial/maximal expiratory flow volume (PEFV/MEFV) maneuvers (used to calculate DI Index) to a maximum change (Δ) in FEV1 of 50% from baseline (MAX). Cough count and dyspnea were measured at each dose. The relation between IOS parameters and DI Index was assessed at baseline and MAX using multivariable linear regression analysis.ResultsCough frequency, dyspnea intensity, and baseline peripheral resistance (R5–R20) were significantly greater in COUGH compared with CONTROL (p = 0.006, p = 0.029, and p = 0.035, respectively). At MAX, the DI Index was significantly lower in COUGH (0.01 ± 0.36) compared with CA (0.67 ± 0.97, p = 0.008), CVA (0.51 ± 0.73, p = 0.012), and CONTROL (0.68 ± 0.45, p = 0.005). Fres and R5–R20 were independent IOS predictors of the DI Index.ConclusionThe bronchodilating effect is impaired in COUGH and preserved in mild CA, CVA, and CONTROL. Increased peripheral airway resistance and decreased resonant frequency are associated with a decreased DI Index. COUGH is a clinical phenotype distinct from healthy normals and asthma.

Predicted values for the forced expiratory flow adjusted for forced vital capacity, a descriptive study

BackgroundThe forced expiratory flows (FEFs) towards the end of the expiration may be more sensitive in detecting peripheral airways obstruction compared to the forced expiratory volume in 1 s and forced vital capacity (FVC). However, they are highly variable. A partial solution is to adjust the FEFs for FVC (FEF/FVC). Here we provide reference equations for these adjusted FEFs at 25%, 50%, 75% and 25–75% of FVC, which are currently lacking.MethodsWe included pulmonary healthy, never-smoker adults; 14 472 subjects from Lifelines, a biobank for health research, and 338 subjects from the department's control cohorts (NORM and Fiddle). Reference equations were obtained by linear regression on 80% of the Lifelines dataset and validated on the remaining data. The best model was defined as the one with the highest adjusted R2-value. The difference in variability between adjusted and unadjusted FEFs was evaluated using the coefficient of variation.ResultsFor all adjusted FEFs, the best model contained age, height and weight. The adjustment improved the coefficient of variation of the FEF75 from 39% to 36% and from 43% to 40%, respectively, in males and females. The highest percentage of explained variance by the reference equation was obtained for FEF75/FVC, 32%–38% for males, and 41%–46% for females, depending on the validation set.ConclusionWe developed reference equations for FVC-adjusted FEF values. We demonstrated minimally yet significantly improved variability. Future studies in obstructive airway diseases should demonstrate whether it is worthwhile to use these (predicted) adjusted FEF values.

Airway mechanics after withdrawal of a leukotriene receptor antagonist in children with mild persistent asthma: Double-blind, randomized, cross-over study.

To determine the response of airway mechanics and the changes in asthma symptoms to stepping down of leukotriene receptor antagonist (LTRA) therapy. Thirty children (mean age: 7.1 years) with mild, well-controlled, and persistent asthma who took LTRA as maintenance treatment were randomized into a double-blind, placebo-controlled, cross-over study. Each group received an LTRA (montelukast) or placebo daily for 2 weeks, followed by a 1-week washout period, and then the alternate treatment for 2 weeks. Spirometry and impulse oscillation system (IOS) measurements before and after four puffs of salbutamol inhalation, fractional exhaled nitric oxide (FeNO), and the childhood asthma control test (C-ACT) were evaluated at baseline, the end of placebo treatment, and the end of LTRA treatment. Changes of FEV1 /FVC (p = .113) and FEV1 (p = .109) from baseline to posttreatment did not differ significantly between the placebo and montelukast groups. In the placebo group, prebronchodilator (pre-) FEV1 /FVC was decreased (83% vs. 86%) and bronchodilator response (BDR) in FEV1 was diminished (10.7% vs. 6.4%) at posttreatment compared with baseline. However, the montelukast group had no significant changes in pre-FEV1 /FVC (p = .865) and BDR in FEV1 (p = .461). In addition, compared with the montelukast group, the placebo group showed no significant changes in Rrs5 (total airway resistance), Rrs5-20 (peripheral airway resistance), FeNO, and symptoms by the C-ACT. In children with well-controlled mild persistent asthma, changes in spirometry, IOS, FeNO, and C-ACT results did not differ between the placebo and montelukast groups within 2 weeks.

Feasibility of Ultra-Low-Dose CT for Bronchoscopy of Peripheral Lung Lesions.

Background and objectives: Thin-section computed tomography (CT) is essential for identifying small bronchi during bronchoscopy using radial endobronchial ultrasound. Some patients should receive an additional CT for a thin-section image. We performed a retrospective study with a prospectively collected database to identify the optimal radiation dose for thin-section CT during peripheral bronchoscopy. Materials and Methods: In total, 91 patients with peripheral lung lesions underwent thin-section CT (both standard CT as a reference and ultra-low-dose CT (ultra-LDCT)). The patients were randomly assigned to one of four groups according to the ultra-LDCT parameters: group 1 = 120 kVp, 25 mAs; group 2 = 100 kVp, 15 mAs; group 3 = 120 kVp, 5 mAs; and group 4 = 100 kVp, 5 mAs. Two radiologists and two physicians analyzed both the standard CT and ultra-LDCT. Results: The effective doses (EDs) of ultra-LDCT significantly differed among the four groups (median EDs were 0.88, 0.34, 0.19, and 0.12 mSv for groups 1–4, respectively; p < 0.001). Median differences in peripheral airway wall thickness were higher in group 4 than in other groups (differences in median wall thickness measured by two radiologists were 0.4–0.5 mm and 0.8–0.9 mm for groups 1–3 and group 4, respectively). Bronchus signs on ultra-LDCT in groups 1 and 2 were well correlated with those of the standard-dose CT (accuracies of two radiologists and two pulmonary physicians were 95–100%). Conclusions: Our results indicate that ultra-LDCT with ED of >0.34 mSv (ED of group 2) is feasible for peripheral bronchoscopy.

Effect of Smoking on FEF 25, FEF 50 &amp; FEF 75 in Adult Male Smokers

Introduction:Smoking is most common in East Asia, where two thirds of all adult males smoke tobacco; cigarette smoking is by far the most common. Smoking is the primary cause of chronic obstructive lung disease, chronic bronchitis and other respiratory symptoms. Many studies have shown significant changes of Forced Expiratory Flow (FEF) as FEF 25, FEF 50 and FEF 75 (L/sec) in adult male smokers. Its objective is to assess the change of FEF 25, FEF 50 and FEF 75 (L/sec) in adult male smokers.&#x0D; Materials and Methods: This cross-sectional comparative study was carried out in the Department of Physiology, Dhaka Medical College, Dhaka during the period of July, 2007 to June, 2008. In the present study 30 adult male smokers consuming cigarettes for more than 5 years selected as study group (Group-B) and were matched with 30 adult males who were non-smokers considered as control group (Group-A) for comparison. FEF 25, FEF 50 and FEF 75 (L/sec) were estimated in both Groups. Analysis of data was done with the help of computer by SPSS 12.0 programmer and significant tests were done by unpaired Student’s “t” test.&#x0D; Results: There were statistically significant differences of FEF25, FEF50 and FEF75 (L/sec) in group A vs. group B.&#x0D; Conclusion: From the statistical analysis of the results obtained in the present study and their comparison with those of published reports, it may be concluded that smoking causes significant change of FEF 25, FEF 50 and FEF 75 (L/sec) among the smokers that could be useful in early diagnosis of peripheral airway obstruction.&#x0D; Medicine Today 2020 Vol.32(2): 81-84

Lung function testing assessment by impulse oscillometry in chronic lung disease

Abstract Impulse oscillometry (IOS) is a variant of forced oscillation technique described by Dubois 50 years ago, which allows us to measure the reactance of the airways and the resistance of the small and large airways during tidal breathing. It requires minimal patient cooperation from subjects who are unable to perform spirometry, like elders, children and patients with neurologic disorders. IOS can outline the diagnosis of obstructive airway disease, differentiate small airway obstruction from large airway obstruction. It is more sensitive than spirometry for peripheral airway disease in determining the severity of the disease, the exacerbations and evaluate the therapeutic response. Other applications include early evaluation of transplant rejection, cystic fibrosis, vocal cord disorder, bronchiectasis, hypersensitivity pneumonitis, obstructive sleep apnea.

Functionally weighted airway sparing (FWAS): a functional avoidance method for preserving post-treatment ventilation in lung radiotherapy

Recent changes to the guidelines for screening and early diagnosis of lung cancer have increased the interest in preserving post-radiotherapy lung function. Current investigational approaches are based on spatially mapping functional regions and generating regional avoidance plans that preferentially spare highly ventilated/perfused lung. A potentially critical, yet overlooked, aspect of functional avoidance is radiation injury to peripheral airways, which serve as gas conduits to and from functional lung regions. Dose redistribution based solely on regional function may cause irreparable damage to the ‘supply chain’. To address this deficiency, we propose the functionally weighted airway sparing (FWAS) method. FWAS (i) maps the bronchial pathways to each functional sub-lobar lung volume; (ii) assigns a weighting factor to each airway based on the relative contribution of the sub-volume to overall lung function; and (iii) creates a treatment plan that aims to preserve these functional pathways. To evaluate it, we used four cases from a retrospective cohort of SAbR patients treated for lung cancer. Each patient’s airways were auto-segmented from a diagnostic-quality breath-hold CT using a research virtual bronchoscopy software. A ventilation map was generated from the planning 4DCT to map regional lung function. For each terminal airway, as resolved by the segmentation software, the total ventilation within the sub-lobar volume supported by that airway was estimated and used as a function-based weighting factor. Upstream airways were weighted based on the cumulative volumetric ventilation supported by corresponding downstream airways. Using a previously developed model for airway radiosensitivity, dose constraints were determined for each airway corresponding to a <5% probability of airway collapse. Airway dose constraints, ventilation scores, and clinical dose constraints were input to a swarm optimization–based inverse planning engine to create a 3D conformal SAbR plan (CRT). The FWAS plans were compared to the patients’ prescribed CRT clinical plans and the inverse-optimized clinical plans. Depending on the size and location of the tumour, the FWAS plan showed superior preservation of ventilation due to airflow preservation through open pathways (i.e. cumulative ventilation score from the sub-lobar volumes of open pathways). Improvements ranged between 3% and 23%, when comparing to the prescribed clinical plans, and between 3% and 35%, when comparing to the inverse-optimized clinical plans. The three plans satisfied clinical requirements for PTV coverage and OAR dose constraints. These initial results suggest that by sparing pathways to high-functioning lung subregions it is possible to reduce post-SAbR loss of respiratory function.

Diagnostic usefulness of impulse oscillometry in adult asthmatics with normal lung function

Although conventional spirometry has been used for diagnosing asthma. Clinician should have to serially follow up spirometry during management to confirm variable airflow limitation. However, spirometry have limitations to evaluate asthmatics who have normal lung function. We evaluated diagnostic usefulness of impulse oscillometry (IOS) that could detect peripheral airway impairment relatively early in these patients. Six hundred-eight patients who have had chronic cough over two months were enrolled. All patients underwent spirometry and IOS. Among them, 48 patients were excluded due to underlying lung disease or chronic obstructive lung disease. One hundred-two patients of asthma were excluded due to decreased lung function (predicted forced expiratory volume in 1 second < 80%). Two-hundred sixty asthmatics with normal lung function were compared with 195 non-asthmatic patients. Diagnosis of asthma was made by allergy specialists. Mean values of AX (reactance area) (non-asthmatics vs. asthmatics with normal lung function, 0.36+/-0.21 vs. 0.88+/-0.81), Fres (resonance frequency) (13.21+/-2.91 vs. 15.83+/-6.98), R5 (resistance at 5 Hz) (0.30+/-0.09 vs. 0.39+/-0.14), R20 (resistance at 20 Hz) (0.23+/-0.07 vs. 0.27+/-0.08), R5-R20 (difference between R5 and R20) (0.27+/-0.07 vs. 0.33+/-0.10), X5 (reactance at 5 Hz) (-0.1+/-0.04 vs. -0.15+/-0.09)and Z5 (respiratory impedance at 5 Hz) (0.32+/-0.09 vs. 0.42+/-0.15) were significantly higher in asthmatics than non-asthmatic patients. AX was the most appropriate value for predicting asthma (the area under a receiver operating characteristic curve = 0.745). Optimal cut-off value for AX to diagnose asthma was 0.85. Its sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 39.23%, 97.44%, 95.33%, and 54.60%, respectively. AX also showed significant relationship with asthma in logistic regression (odds ratio: 41.24, p < 0.001). One-point measure of AX (over 0.85) could assist to diagnosis of asthma when patient showed normal lung function at initial visit.

The role of electromagnetic navigational bronchoscopy in the era of robotics

The advent of the superDimension (Medtronic Corporation, Minneapolis, MN, USA) electromagnetic navigation bronchoscopy (ENB) offers bronchoscopists specialized navigation software to create a 3-dimensional map to target peripheral pulmonary nodules. A pervasive criticism of ENB has centered around the reliance on virtual targets and catheter deflection. The presence of CT-to-body divergence is a critical concern when attempting to ensure that the virtual target truly represents the target lesion. Attempts to make up for the shortcomings of ENB have resulted in development of multiple robotic bronchoscopic platforms. Robotically guided bronchoscopy platforms typically feature smaller scopes that are used to navigate through the small, peripheral airways using automated arms. The ability to successfully biopsy peripheral lung nodules will continue to improve as both the ENB platforms and robotic bronchoscopy platforms evolve. A central question to the future of biopsy platforms is whether one is preferred over the other.