The objectives of the present study were to evaluate the discriminating power of spirometric and plethysmographic lung function parameters to differenciate the diagnosis of asthma, ACO, COPD, and to ...define functional characteristics for more precise classification of obstructive lung diseases. From the databases of 4 centers, a total of 756 lung function tests (194 healthy subjects, 175 with asthma, 71 with ACO, 78 with COPD and 238 with CF) were collected, and gradients among combinations of target parameters from spirometry (forced expiratory volume one second: FEV1; FEV1/forced vital capacity: FEV1/FVC; forced expiratory flow between 25-75% FVC: FEF25-75), and plethysmography (effective, resistive airway resistance: sReff; aerodynamic work of breathing at rest: sWOB), separately for in- and expiration (sReffIN, sReffEX, sWOBin, sWOBex) as well as static lung volumes (total lung capacity: TLC; functional residual capacity: FRCpleth; residual volume: RV), the control of breathing (mouth occlusion pressure: P0.1; mean inspiratory flow: VT/TI; the inspiratory to total time ratio: TI/Ttot) and the inspiratory impedance (Zinpleth = P0.1/VT/TI) were explored. Linear discriminant analyses (LDA) were applied to identify discriminant functions and classification rules using recursive partitioning decision trees. LDA showed a high classification accuracy (sensitivity and specificity > 90%) for healthy subjects, COPD and CF. The accuracy dropped for asthma (~70%) and even more for ACO (~60%). The decision tree revealed that P0.1, sRtot, and VT/TI differentiate most between healthy and asthma (68.9%), COPD (82.1%), and CF (60.6%). Moreover, using sWOBex and Zinpleth ACO can be discriminated from asthma and COPD (60%). Thus, the functional complexity of obstructive lung diseases can be understood, if specific spirometric and plethysmographic parameters are used. Moreover, the newly described parameters of airway dynamics and the central control of breathing including Zinpleth may well serve as promising functional marker in the field of precision medicine.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BackgroundThe plethysmographic shift volume–flow loop (sRaw-loop) measured during tidal breathing allows the determination of several lung function parameters such as the effective specific airway ...resistance (sReff), calculated from the ratio of the integral of the resistive aerodynamic specific work of breathing (sWOB) and the integral of the corresponding flow–volume loop. However, computing the inspiratory and expiratory areas of the sRaw-loop separately permits the determination of further parameters of airway dynamics. Therefore, we aimed to define the discriminating diagnostic power of the inspiratory and expiratory sWOB (sWOBin, sWOBex), as well as of the inspiratory and expiratory sReff (sReff IN and sReff EX), for discriminating different functional phenotypes of chronic obstructive lung diseases.MethodsReference equations were obtained from measurement of different databases, incorporating 194 healthy subjects (35 children and 159 adults), and applied to a collective of 294 patients with chronic lung diseases (16 children with asthma, aged 6–16 years, and 278 adults, aged 17–92 years). For all measurements, the same type of plethysmograph was used (Jaeger Würzburg, Germany).ResultsBy multilinear modelling, reference equations of sWOBin, sWOBex, sReff IN and sReff EX were derived. Apart from anthropometric indices, additional parameters such as tidal volume (VT), the respiratory drive (P0.1), measured by means of a mouth occlusion pressure measurement 100 ms after inspiration and the mean inspiratory flow (VT/TI) were found to be informative. The statistical approach to define reference equations for parameters of airway dynamics reveals the interrelationship between covariants of the actual breathing pattern and the control of breathing.ConclusionsWe discovered that sWOBin, sWOBex, sReff IN and sReff EX are new discriminating target parameters, that differentiate much better between chronic obstructive diseases and their subtypes, especially between chronic obstructive pulmonary disease (COPD) and asthma–COPD overlap (ACO), thus strengthening the concept of precision medicine.
Effective specific airway resistance (sReff), its reciprocal the effective specific airway conductance (sGeff) are computed as ratios between the integral of the resistive aerodynamic work of ...breathing (sWOB) and the integral of the tidal flow/volume loop, the reciprocal, respectively. Unfortunately, reference equations to obtain normative values for sReff, sGeff, and sWOB are not yet available. To assess reference equations for sWOB, sReff, and sGeff during tidal breathing at resting level in healthy infants, children, and adults by a multidimensional model. Retrospectively exported data were collected from databases of five Swiss lung function centers, in which plethysmography (Jaeger Würzburg, Germany) was performed for the assessment of airway dynamics, static lung volumes, and forced breathing flow‐volume loops, in a collective of 28 healthy infants, 47 children, and 273 adults. From this cohort, reference equations were computed based on anthropometric measures, lung volumes, indices of the breathing pattern, and timing of breathing. By multi‐linear modeling reference equations of sReff, sGeff, and sWOB could be defined taking as independent parameters apart from anthropometric parameters, also parameters given by the ratio between the tidal volume and functional residual capacity (FRCpleth/VT), and the ratio between VT and inspiratory time (VT/TI). An alternative statistical approach to define reference equations of airway dynamics reveals that apart from the subject's anthropometric measurements, parameters of the magnitude of static lung volumes, the breathing pattern, and the timing of breathing are co‐variants of reference equations of airway dynamics over a large age range.
By the work presented, the gap of the effectiveness regarding the embodiment of airway dynamics in the assessment of functional severity in various diseases can be bridged.
There are few studies comparing diagnostic accuracy of different lung function parameters evaluating dose-response characteristics of methacholine (MCH) challenge tests (MCT) as quantitative outcome ...of airway hyperreactivity (AHR) in asthmatic patients. The aim of this retrospectively analysis of our database (Clinic Barmelweid, Switzerland) was, to assess diagnostic accuracy of several lung function parameters quantitating AHR by dose-response characteristics.
Changes in effective specific airway conductance (sG
) as estimate of the degree of bronchial obstruction were compared with concomitantly measured forced expiratory volume in 1 s (FEV
) and forced expiratory flows at 50% forced vital capacity (FEF
). According to the GINA Guidelines the patients (n = 484) were classified into asthmatic patients (n = 337) and non-asthmatic subjects (n = 147). Whole-body plethysmography (CareFusion, Würzburg, Germany) was performed using ATS-ERS criteria, and for the MCTs a standardised computer controlled protocol with 3 consecutive cumulative provocation doses (PD
: 0.2 mg; PD
: 1.0 mg; PD
: 2.2 mg) was used. Break off criterion for the MCTs were when a decrease in FEV
of 20% was reached or respiratory symptoms occurred.
In the assessment of AHR, whole-body plethysmography offers in addition to spirometry indices of airways conductance and thoracic lung volumes, which are incorporated in the parameter sG
, derived from spontaneous tidal breathing. The cumulative percent dose-responses at each provocation step were at the 1
level step (0.2 mg MCH) 3.7 times, at the 2
level step (1 mg MCH) 2.4 times, and at the 3
level step (2.2 mg MCH) 2.0 times more pronounced for sG
, compared to FEV
. A much better diagnostic odds ratio of sG
(7.855) over FEV
(6.893) and FEF
(4.001) could be found. Moreover, the so-called dysanapsis, and changes of end-expiratory lung volume were found to be important determinants of AHR.
Applying plethysmographic tidal breathing analysis in addition to spirometry in MCTs provides relevant advantages. The absence of deep and maximal inhalations and forced expiratory manoeuvres improve the subject's cooperation and coordination, and provide sensitive and differentiated test results, improving diagnostic accuracy. Moreover, by the combined assessment, pulmonary hyperinflation and dysanapsis can be respected in the differentiation between "asthmatics" and "non-asthmatics".
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This abstract was unintentionally published twice in this supplement 1, by the same authors. Following should be considered the version of record and used for citation purposes: “Mark Richard Kraemer ...and Bermans J. Iskandar, The Wisconsin Hydrocephalus Survey: shunt-dependent hydrocephalus management style among members of the American Society of Pediatric Neurosurgeons, Fluids and Barriers of the CNS, Volume 12, Supplement Issue 1, 10.1186/2045-8118-12-S1-O12”. The duplicate “Mark Richard Kraemer and Bermans J. Iskandar, The Wisconsin Hydrocephalus Survey: shunt-dependent hydrocephalus management style among members of the American Society of Pediatric Neurosurgeons, Fluids and Barriers of the CNS, Volume 12, Supplement Issue 1, https://doi.org/10.1186/2045-8118-12-S1-O35” is to be ignored. Springer apologizes to the readers of the journal for not detecting the duplication during the publication process.
Functional deterioration in cystic fibrosis (CF) may be reflected by increasing bronchial obstruction and, as recently shown, by ventilation inhomogeneities. This study investigated which ...physiological factors (airway obstruction, ventilation inhomogeneities, pulmonary hyperinflation, development of trapped gas) best express the decline in lung function, and what role specific CFTR genotypes and different types of bronchial infection may have upon this process.
Serial annual lung function tests, performed in 152 children (77 males; 75 females) with CF (age range: 6-18 y) provided data pertaining to functional residual capacity (FRCpleth, FRCMBNW), volume of trapped gas (VTG), effective specific airway resistance (sReff), lung clearance index (LCI), and forced expiratory indices (FVC, FEV1, FEF50).
All lung function parameters showed progression with age. Pulmonary hyperinflation (FRCpleth > 2SDS) was already present in 39% of patients at age 6-8 yrs, increasing to 67% at age 18 yrs. The proportion of patients with VTG > 2SDS increased from 15% to 54% during this period. Children with severe pulmonary hyperinflation and trapped gas at age 6-8 yrs showed the most pronounced disease progression over time. Age related tracking of lung function parameters commences early in life, and is significantly influenced by specific CFTR genotypes. The group with chronic P. aeruginosa infection demonstrated most rapid progression in all lung function parameters, whilst those with chronic S. aureus infection had the slowest rate of progression. LCI, measured as an index of ventilation inhomogeneities was the most sensitive discriminator between the 3 types of infection examined (p < 0.0001).
The relationships between lung function indices, CFTR genotypes and infective organisms observed in this study suggest that measurement of other lung function parameters, in addition to spirometry alone, may provide important information about disease progression in CF.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In patients with cystic fibrosis (CF) the architecture of the developing lungs and the ventilation of lung units are progressively affected, influencing intrapulmonary gas mixing and gas exchange. We ...examined the long-term course of blood gas measurements in relation to characteristics of lung function and the influence of different CFTR genotype upon this process.
Serial annual measurements of PaO2 and PaCO2 assessed in relation to lung function, providing functional residual capacity (FRCpleth), lung clearance index (LCI), trapped gas (VTG), airway resistance (sReff), and forced expiratory indices (FEV1, FEF50), were collected in 178 children (88 males; 90 females) with CF, over an age range of 5 to 18 years. Linear mixed model analysis and binary logistic regression analysis were used to define predominant lung function parameters influencing oxygenation and carbon dioxide elimination.
PaO2 decreased linearly from age 5 to 18 years, and was mainly associated with FRCpleth, (p < 0.0001), FEV1 (p < 0.001), FEF50 (p < 0.002), and LCI (p < 0.002), indicating that oxygenation was associated with the degree of pulmonary hyperinflation, ventilation inhomogeneities and impeded airway function. PaCO2 showed a transitory phase of low PaCO2 values, mainly during the age range of 5 to 12 years. Both PaO2 and PaCO2 presented with different progression slopes within specific CFTR genotypes.
In the long-term evaluation of gas exchange characteristics, an association with different lung function patterns was found and was closely related to specific genotypes. Early examination of blood gases may reveal hypocarbia, presumably reflecting compensatory mechanisms to improve oxygenation.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The relationship between sensitization to Aspergillus fumigatus and progression of pulmonary function is not yet established in cystic fibrosis (CF).
We aimed to evaluate onset of A. fumigatus ...sensitization and development of allergic bronchopulmonary aspergillosis (ABPA), as well as to determine the physiologic factors of lung function influencing these mechanisms in CF.
Serial annual lung function tests performed in 122 children with CF (62 males; 60 females; age: 6-18 yr) provided data pertaining to FRC measured by plethysmography, lung clearance index, volume of trapped gas, effective specific airway resistance, and forced expiratory indices (FEV1, FEF at 50% VC). Specific IgE to recombinant A. fumigatus allergens, rAspf1 and rAspf3, served as marker for sensitization, and to rAspf4 and rAspf6 as indications for a serologic ABPA, were clinically diagnosed (Nelson criteria). By linear mixed-effect model analysis, five patient groups, (1) not sensitized and free from Pseudomonas aeruginosa, (2) intermittently P. aeruginosa colonized, (3) chronically P. aeruginosa infected, (4) sensitized, and (5) with ABPA, were retrospectively evaluated.
A. fumigatus sensitization was best reflected by increased rAspf1+3-specific IgE levels, whereas, in most patients, sensitization was preceded by P. aeruginosa infection. Patients with ABPA demonstrated the most severe progression in all lung function parameters, and FEF at 50% VC, volume of trapped gas, and effective specific airway resistance were the best predictors (p < 0.0001). However, regarding distinction between sensitization to A. fumigatus and development of ABPA in the course of CF, chronic P. aeruginosa infection has to be taken into account.
Airway narrowing, gas trapping, and small airway disease are the major targets for functional derangement in ABPA.
Maternal smoking in pregnancy is associated with respiratory diseases in the offspring, possibly due to prenatal influences on the developing immune system. We investigated whether maternal smoking ...in pregnancy was associated with cord blood leukocyte numbers, including precursor dendritic cells, adjusting for concomitant factors. In a prospective healthy birth cohort study, total leukocyte counts were reduced in neonates of smoking mothers 10.7 (8.4-13.0), n=14 compared with nonexposed infants 14.7 (13.7-15.7), n=74, p=0.002 geometric mean cells x 10(3)/microL (95% confidence interval). All leukocyte subsets were decreased, most prominently segmented neutrophils 4.3 (2.8-5.7) versus 6.2 (5.5-6.8), p=0.021, lymphocytes 3.8 (2.9-4.8) versus 5.0 (4.5-5.6), p=0.036, and myeloid precursor dendritic cells 12.7 cells/microL (9.1-17.8) versus 18.3 (15.8-21.2), p=0.055. These differences persisted after adjustment for possible confounders. Predictors of myeloid precursor dendritic cell numbers in multivariable models were maternal smoking (-5.1 cells/microL, p=0.042), age (-0.5 cells/microL/y, p=0.035), and, marginally, asthma (+8.1 cells/microL, p=0.075). The decrease of all leukocytes in neonates of smoking mothers could be clinically significant and suggests a decreased cell production, increased peripheral recruitment, or retention in bone marrow. Given the importance of dendritic cells in early immune responses, their decrease might reflect an impact of maternal smoking on the developing fetal immune system.
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