Predicting parameters of airway dynamics generated from inspiratory and expiratory plethysmographic airway loops, differentiating subtypes of chronic obstructive diseases

Abstract

Background: The plethysmographic shift volume-flow loop (sR_aw-loop) measured during tidal breathing allows the determination of several lung function parameters such as the effective specific airway resistance (sR_eff), 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 sR_aw-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 (sWOB_in, sWOB_ex), as well as of the inspiratory and expiratory sR_eff (sR_eff ^IN and sR_eff ^EX), for discriminating different functional phenotypes of chronic obstructive lung diseases.

Methods: Reference 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).

Results: By multilinear modelling, reference equations of sWOB_in, sWOB_ex, sR_eff ^IN and sR_eff ^EX were derived. Apart from anthropometric indices, additional parameters such as tidal volume (V_T), the respiratory drive (P_0.1), measured by means of a mouth occlusion pressure measurement 100 ms after inspiration and the mean inspiratory flow (V_T/T_I) 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.

Conclusions: We discovered that sWOB_in, sWOB_ex, sR_eff ^IN and sR_eff ^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.

Keywords: Asthma; COPD Pathology; Equipment Evaluations; Lung Physiology; Respiratory Function Test.

Figure 1

Aerodynamic parameters computed by integrals from a plethysmographic shift volume–tidal flow loop (sR_aw-loop) obtained from a patient with COPD, separated into the inspiratory and expiratory limb of the loop. EELV, end-expiratory lung volume; FRC_pleth, functional residual capacity; sR_eff, effective specific airways resistance; sR_eff ^EX, expiratory, effective specific airways resistance; sR_eff ^IN, inspiratory, effective specific airways resistance; sWOB, resistive aerodynamic work of breathing; sWOB_in, resistive aerodynamic work of breathing integrated from the inspiratory part of the R_aw-loop; sWOB_ex, resistive aerodynamic work of breathing integrated from the expiratory part of sR_aw-loop; V_pleth plethysmographic shift volume; ∆V₀, difference between inspiratory and expiratory shift-volume at FRC_pleth.

Figure 2

Age distributions of sWOB, in relation to sWOB_in (A) and sWOB_ex (B) and sR_eff ^IN in relation to sR_eff ^EX (C), over the age range of 6–86 years for healthy subjects in absolute terms. sWOB, resistive aerodynamic work of breathing; sWOB_ex, resistive aerodynamic work of breathing integrated from the expiratory part of sR_aw-loop; sWOB_in, resistive aerodynamic work of breathing integrated from the inspiratory part of the R_aw-loop; sR_eff, effective specific airway resistance; sR_eff ^EX, expiratory, effective specific airways resistance; sR_eff ^IN, inspiratory, effective specific airways resistance.

Figure 3

Z-score distribution of each lung function parameter within the three diagnostic classes. ACO, asthma–COPD overlap; COPD, chronic obstructive pulmonary disease; FEF_25–75, forced expiratory flow between 25% and 75% vital capacity; FEV₁, forced expiratory volume in 1 s; FRC_pleth, plethysmographic functional residual capacity; FVC, forced vital capacity; P_0.1, respiratory drive; RV, reserve volume; sR_eff, effective specific airway resistance; sR_eff ^EX, expiratory, effective specific airways resistance; sR_eff ^IN, inspiratory, effective specific airways resistance; sWOB, resistive aerodynamic work of breathing; sWOB_ex, resistive aerodynamic work of breathing integrated from the expiratory part of sR_aw-loop; sWOB_in, resistive aerodynamic work of breathing integrated from the inspiratory part of the R_aw-loop; TLC, total lung capacity; V_T/T_I, mean inspiratory flow.

Figure 4

Linear discriminant analysis based on all 10 parameters from which by stepwise exclusion 6 remained in the model (sR_tot, sWOB_ex, sR_eff, sWOB_in, sR_eff ^IN and sR_eff ^EX), differentiating between asthma, ACO and COPD. ACO, asthma–COPD overlap; COPD, chronic obstructive pulmonary disease; sR_eff, effective specific airway resistance; sR_eff ^EX, expiratory, effective specific airways resistance; sR_eff ^IN, inspiratory, effective specific airways resistance; sWOB_ex, resistive aerodynamic work of breathing integrated from the expiratory part of sR_aw-loop; sWOB_in, resistive aerodynamic work of breathing integrated from the inspiratory part of the R_aw-loop.