The DS-14 questionnaire: psychometric characteristics and utility in patients with obstructive sleep apnea.

Little is known about type D personality in patients with obstructive sleep apnea (OSA). The DS-14 questionnaire is the standard tool to assess this personality type, but it has not been properly validated in patients with OSA, nor has it been correlated with clinical features in these patients. PURPOSE: To determine the internal consistency and test-retest reliability of the DS-14 questionnaire, as well as the prevalence of type D personality in the overall OSA sample and subgroups. We assessed the influence of type D on perceived symptoms and its congruence with self-reported measures of personality, depression, fatigue, anxiety, quality of life, and quality of sleep. METHODS: Patients with OSA completed the DS-14 questionnaire, Big Five Inventory-2 questionnaire, Hospital Anxiety and Depression Scale, SF-36 Health Survey Questionnaire, Epworth Sleepiness Scale and Stanford Sleepiness Scale, Pittsburgh Sleep Quality Index and Insomnia Severity Index, Fatigue Assessment Scale, and Checklist Individual Strength. After 1 month, the DS-14 questionnaire was repeated. RESULTS: The overall prevalence of type D personality was 32%. Internal consistency (negative affectivity: α = 0.880, social inhibition: α = 0.851) and diagnostic test-retest reliability (kappa value = 0.664) of the DS-14 questionnaire were high. Significantly more symptoms of anxiety, depression, poor sleep quality, fatigue, and a worse health perception were found in OSA with type D. Neither OSA severity nor REM predominance altered these observations. CONCLUSION: The DS-14 questionnaire showed excellent psychometric properties in patients with OSA. The prevalence of type D personality in patients with OSA was higher than in the general population. The presence of type D personality was associated with higher symptom burden.

Getting the Most out of Spirometry: A Tool to Guide Dry Powder Inhaler Use.

BACKGROUND: Dry powder inhaler (DPI) use requires sufficient peak inspiratory flow over the DPI internal resistance (PIFR). OBJECTIVES: We examined whether spirometric peak inspiratory flow (PIFspiro) could serve to predict PIFR in patients with obstructive lung disease. METHOD: Thirty healthy nonsmokers and 140 stable outpatients (70 COPD, 70 asthma) performed spirometry according to the 2019 ERS/ATS spirometry update, yielding PIFspiro. Using a PIFR measurement device with varying orifices, all subjects' PIFR values were recorded for 5 predefined resistance levels, characterized by 5 orifice cross sections (SR). A test group including all healthy subjects, 30 of the asthma, and 30 of the COPD patients was used to establish the relationship between PIFR and both PIFspiro and SR by multiple regression. A validation group including the remaining 40 asthma and 40 COPD patients, served to verify whether their predicted PIFR value corresponded to the measured PIFR for each resistance level. RESULTS: The asthma (FEV1 = 78 ± 17 [SD] %pred) and COPD (FEV1 = 46 ± 17 [SD] %pred) patients under study had varying airway obstruction. In the test group, PIFR could be predicted by ln[PIFspiro] (p < 0.0001), SR (p < 0.0001), and SR2 (p = 0.006), with an adjusted R2 = 0.71. In the validation group, estimated PIFR did not significantly differ from measured PIFR (p > 0.05 for the 5 resistance levels). CONCLUSIONS: We propose a simple method to predict PIFR for a range of common DPI resistances, based on the device characteristics and on the patient's characteristics reflected in PIFspiro. As such, routine spirometry can serve to estimate a patient's specific PIFR without the need for additional testing.

Fractal analysis reveals functional unit of ventilation in the lung.

Ventilation is inhomogeneous in the lungs across species. It has been hypothesized that ventilation inhomogeneity is largely determined by the design of the airway branching network. Because exchange of gases at the alveolar barrier is more efficient when gas concentrations are evenly distributed at subacinar length scales, it is assumed that a 'functional unit' of ventilation exists within the lung periphery, where gas concentration becomes uniform. On the other hand, because the morphology of pulmonary airways and alveoli, and the distribution of inhaled fluorescent particles show self-similar fractal properties over a wide range of length scales, it has been predicted that fractal dimension of ventilation approaches unity within an internally homogeneous functional unit of ventilation. However, the existence of such a functional unit has never been demonstrated experimentally due to lack of in situ gas concentration measurements of sufficient spatial resolution in the periphery of a complex bifurcating network. Here, using energy-subtractive synchrotron radiation tomography, we measured the distribution of an inert gas (Xe) in the in vivo rabbit lung during Xe wash-in breathing manoeuvres. The effects of convective flow rate, diffusion and cardiac motion were also assessed. Fractal analysis of resulting gas concentration and tissue density maps revealed that fractal dimension was always smaller for Xe than for tissue density, and that only for the gas, a length scale existed where fractal dimension approached unity. The length scale where this occurred was seen to correspond to that of a rabbit acinus, the terminal structure comprising only alveolated airways. KEY POINTS: Gas ventilation is inhomogeneous in the lung of many species. However, it is not known down to what length scales this inhomogeneity persists. It is generally assumed that ventilation becomes homogeneous at subacinar length scales, beyond the spatial resolution of commonly available imaging techniques, hence this has not been demonstrated experimentally. Here we measured the distribution of inhaled Xe gas in the rabbit lung using synchrotron radiation energy-subtractive imaging and used fractal analysis to show that ventilation becomes internally uniform within regions about the size of rabbit lung acini.

Peak In- and Expiratory Flow Revisited: Reliability and Reference Values in Adults.

BACKGROUND: While peak in- and expiratory flow rates offer valuable information for diagnosis and monitoring in respiratory disease, these indices are usually considered too variable to be routinely used for quantification in clinical practice. OBJECTIVES: The aim of the study was to obtain reproducible measurements of maximal inspiratory flow rates and to construct reference equations for peak in- and expiratory flows (PIF and PEF). METHOD: With coaching for maximal effort, 187 healthy Caucasian subjects (20-80 years) performed at least 3 combined forced inspiratory and expiratory manoeuvres, until at least 2 peak inspiratory flow measurements were within 10% of each other. The effect on PIF preceded by a slow expiration instead of a forced expiration and PIF repeatability over 3 different days was also investigated in subgroups. Reference values and limits of normal for PIF, mid-inspiratory flow, and PEF were obtained according to the Lambda-Mu-Sigma statistical method. RESULTS: A valid PIF could be obtained within 3.3 ± 0.6(SD) attempts, resulting in an overall within-test PIF variability of 4.6 ± 3.2(SD)%. A slow instead of a forced expiration prior to forced inspiration resulted in a significant (p < 0.001) but small PIF increase (2.5% on average). Intraclass correlation coefficient for between-day PIF was 0.981 (95% CI: 0.960-0.992). Over the entire age range, inter-subject PIF variability was smaller than in previous reports, and PIF could be predicted based on its determinants gender, age, and height (r2 = 0.53). CONCLUSIONS: When adhering to similar criteria for the measurement of effort-dependent portions of inspiratory and expiratory flow-volume curves, performed according to current ATS/ERS standards, it is possible to obtain reproducible PIF and PEF values for use in routine clinical practice.

Aligning Lung Function Equipment and Reference Values in Adults.

BACKGROUND: When introducing new equipment or reference equations into the lung function laboratory, systematic z-score deviations could arise due to local differences in population or equipment. OBJECTIVE: To propose a workable method for aligning reference equations with lung function equipment. METHOD: Using two cases of equipment transition in our laboratory as a test case, we first performed lung function testing after the transition, on a control group of 40 normal young adults (20 male/20 female; 20-30 years old). For those indices with an average z-score in excess of ±0.5, adapted reference values were obtained by an offset or scaling factor on the M coefficient with the so-called lambda-mu-sigma (LMS) method recommended by the Global Lung Function Initiative, and the z-scores were computed again. RESULTS: Following a transition involving instrumental dead space reduction, the lung clearance index was predictably reduced, resulting in a mean (±SD) z-score of -1.9 (±1.1) in the control group; by adapting the reference values with an offset on M, the z-score became -0.1 (±1.1). Applying the same method to a transition of standard lung function equipment, the z-scores became centered around zero in the control group, but also became properly aligned in a test group of 81 other subjects spanning a wider age range (20-80 years). CONCLUSIONS: We proposed and verified a method for aligning local equipment with reference values obtained elsewhere, or following a local change in equipment. The key is to measure a relatively small young adult group, identifying those lung function indices that need adaptation based on z-scores, in order to then obtain laboratory-specific reference values that can be applied over the entire age range.

The quantitative link of lung clearance index to bronchial segments affected by bronchiectasis.

In adult patients with cystic fibrosis (CF), the lung clearance index (LCI) derived from the multiple breath washout relates to both acinar and conductive ventilation heterogeneity. The latter component predicts an association between LCI and the number of bronchial segments affected by bronchiectasis. Here, we experimentally demonstrated this association in patients with CF, and also examined an ancillary group of patients with non-CF bronchiectasis. We conclude that lung disease severity in terms of number of bronchial segments results in an associated LCI increase, likely constituting a portion of LCI that cannot be reversed by treatment in patients with CF lung disease.

Dynamic Mechanical Interactions Between Neighboring Airspaces Determine Cyclic Opening and Closure in Injured Lung.

OBJECTIVES: Positive pressure ventilation exposes the lung to mechanical stresses that can exacerbate injury. The exact mechanism of this pathologic process remains elusive. The goal of this study was to describe recruitment/derecruitment at acinar length scales over short-time frames and test the hypothesis that mechanical interdependence between neighboring lung units determines the spatial and temporal distributions of recruitment/derecruitment, using a computational model. DESIGN: Experimental animal study. SETTING: International synchrotron radiation laboratory. SUBJECTS: Four anesthetized rabbits, ventilated in pressure controlled mode. INTERVENTIONS: The lung was consecutively imaged at ~ 1.5-minute intervals using phase-contrast synchrotron imaging, at positive end-expiratory pressures of 12, 9, 6, 3, and 0 cm H2O before and after lavage and mechanical ventilation induced injury. The extent and spatial distribution of recruitment/derecruitment was analyzed by subtracting subsequent images. In a realistic lung structure, we implemented a mechanistic model in which each unit has individual pressures and speeds of opening and closing. Derecruited and recruited lung fractions (Fderecruited, Frecruited) were computed based on the comparison of the aerated volumes at successive time points. MEASUREMENTS AND MAIN RESULTS: Alternative recruitment/derecruitment occurred in neighboring alveoli over short-time scales in all tested positive end-expiratory pressure levels and despite stable pressure controlled mode. The computational model reproduced this behavior only when parenchymal interdependence between neighboring acini was accounted for. Simulations closely mimicked the experimental magnitude of Fderecruited and Frecruited when mechanical interdependence was included, while its exclusion gave Frecruited values of zero at positive end-expiratory pressure greater than or equal to 3 cm H2O. CONCLUSIONS: These findings give further insight into the microscopic behavior of the injured lung and provide a means of testing protective-ventilation strategies to prevent recruitment/derecruitment and subsequent lung damage.

Substance deposition assessment in obstructed pulmonary system through numerical characterization of airflow and inhaled particles attributes.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) and asthma are considered as the two most widespread obstructive lung diseases, whereas they affect more than 500 million people worldwide. Unfortunately, the requirement for detailed geometric models of the lungs in combination with the increased computational resources needed for the simulation of the breathing did not allow great progress to be made in the past for the better understanding of inflammatory diseases of the airways through detailed modelling approaches. In this context, computational fluid dynamics (CFD) simulations accompanied by fluid particle tracing (FPT) analysis of the inhaled ambient particles are deemed critical for lung function assessment. Also they enable the understanding of particle depositions on the airways of patients, since these accumulations may affect or lead to inflammations. In this direction, the current study conducts an initial investigation for the better comprehension of particle deposition within the lungs. More specifically, accurate models of the airways obstructions that relate to pulmonary disease are developed and a thorough assessment of the airflow behavior together with identification of the effects of inhaled particle properties, such as size and density, is conducted. Our approach presents a first step towards an effective personalization of pulmonary treatment in regards to the geometric characteristics of the lungs and the in depth understanding of airflows within the airways. METHODS: A geometry processing technique involving contraction algorithms is established and used to employ the different respiratory arrangements associated with lung related diseases that exhibit airways obstructions. Apart from the normal lung case, two categories of obstructed cases are examined, i.e. models with obstructions in both lungs and models with narrowings in the right lung only. Precise assumptions regarding airflow and deposition fraction (DF) over various sections of the lungs are drawn by simulating these distinct incidents through the finite volume method (FVM) and particularly the CFD and FPT algorithms. Moreover, a detailed parametric analysis clarifies the effects of the particles size and density in terms of regional deposition upon several parts of the pulmonary system. In this manner, the deposition pattern of various substances can be assessed. RESULTS: For the specific case of the unobstructed lung model most particles are detected on the right lung (48.56% of total, when the air flowrate is 12.6 L/min), a fact that is also true when obstructions arise symmetrically in both lungs (51.45% of total, when the air flowrate is 6.06 L/min and obstructions occur after the second generation). In contrast, when narrowings are developed on the right lung only, most particles are pushed on the left section (68.22% of total, when the air flowrate is 11.2 L/min) indicating that inhaled medication is generally deposited away from the areas of inflammation. This observation is useful when designing medical treatment of lung diseases. Furthermore, particles with diameters from 1 µm to 10 µm are shown to be mainly deposited on the lower airways, whereas particles with diameters of 20 µm and 30 µm are mostly accumulated in the upper airways. As a result, the current analysis indicates increased DF levels in the upper airways when the particle diameter is enlarged. Additionally, when the particles density increases from 1000 Kg/m3 to 2000 Kg/m3, the DF is enhanced on every generation and for all cases investigated herein. The results obtained by our simulations provide an accurate and quantitative estimation of all important parameters involved in lung modeling. CONCLUSIONS: The treatment of respiratory diseases with inhaled medical substances can be advanced by the clinical use of accurate CFD and FPT simulations and specifically by evaluating the deposition of inhaled particles in a regional oriented perspective in regards to different particle sizes and particle densities. Since a drug with specific characteristics (i.e. particle size and density) exhibits maximum deposition on particular lung areas, the current study provides initial indications to a qualified physician for proper selection of medication.

Transfer factor, lung volumes, resistance and ventilation distribution in healthy adults.

Monitoring of chronic lung disease requires reference values of lung function indices, including putative markers of small airway function, spanning a wide age range.We measured spirometry, transfer factor of the lung for carbon monoxide (TLCO), static lung volume, resistance and ventilation distribution in a healthy population, studying at least 20 subjects per sex and per decade between the ages of 20 and 80 years.With respect to the Global Lung Function Initiative reference data, our subjects had average z-scores for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC of -0.12, 0.04 and -0.32, respectively. Reference equations were obtained which could account for a potential dependence of index variability on age and height. This was done for (but not limited to) indices that are pertinent to asthma and chronic obstructive pulmonary disease studies: forced expired volume in 6 s, forced expiratory flow, TLCO, specific airway conductance, residual volume (RV)/total lung capacity (TLC), and ventilation heterogeneity in acinar and conductive lung zones.Deterioration in acinar ventilation heterogeneity and lung clearance index with age were more marked beyond 60 years, and conductive ventilation heterogeneity showed the greatest increase in variability with age. The most clinically relevant deviation from published reference values concerned RV/TLC values, which were considerably smaller than American Thoracic Society/European Respiratory Society-endorsed reference values.

Bronchiolitis obliterans syndrome leads to a functional deterioration of the acinus post lung transplant.

Bronchiolitis obliterans syndrome (BOS) limits long-term survival of lung transplant recipients, and airflow obstruction in these patients likely originates in the small airways. 61 double lung transplant recipients performed multiple breath nitrogen washouts to obtain indices of acinar and conductive ventilation heterogeneity (Sacin, Scond). There was a significant association of BOS status with Sacin (Kruskal-Wallis; p<0.001) but not with Scond (p=0.1). These results demonstrate that it is the structural alteration of the terminal bronchioles, generating ventilation heterogeneity at the level of the diffusion front, and not the bronchioles located more proximally, that is driving the airflow obstruction that determines BOS status.