Discussion
The shape of the sRaw-loop is quite complex and not a simple narrow oval loop, especially not in patients with obstructive lung diseases. Consequently, different investigators have used different portions of the loop to approximate a representative value for the entire breathing cycle. The effective specific resistance (sReff) and the total specific resistance (sRtot), have been well established,31 45 46 although they have not received sufficient attention in the literature.
The specific work of breathing assessed by plethysmography
A major step in the assessment of airway dynamics throughout the entire plethysmographic shift volume–tidal flow loop and its mathematical understanding of loop shaping was first elaborated by Matthys and Orth.31 They extended the dimensional analysis applied by Jaeger and Otis,47 to integrate these contributions to an ‘effective resistance’ that included the effects of the entire range of variable flows during tidal breathing and non-linearities of the breathing loop. The outstanding feature of these of airway dynamic parameters is their reflection of an integrative assessment of airway behaviour throughout the tidal breathing cycles. The digital integration of the respective loops improves the signal-to-noise ratio.
Findings of the present study
Normative values of the airway dynamic parameters depend not only on anthropometric measures but also on parameters of the breathing pattern, timing of breathing and central control of breathing. This applies not only to sWOB and sReff, as previously reported,30 but also to the inspiratory and expiratory parts of the sRaw-loop, which are indicated by sWOBin, sWOBex, sReff
IN and sReff
EX. Therefore, we postulate, that the effort of breathing to move the lung, and hence the sWOB obtained by plethysmography allows an estimation of the gas dynamic, resistive effort integrating the needed plethysmographic shift volume over the tidal volume. In a constant volume whole-body plethysmograph, the shift volume refers to the size of the lung volume that decreases on compression and increases on decompression, and is proportional to the underpressure and overpressure in the lung and the absolute, ventilated and non-ventilated, lung volume. It follows that the specific gas-dynamic work performed during tidal breathing at rest can be estimated by simultaneously assessing the plethysmographic shift volume and the corresponding tidal volume. By this way, the sWOB can be considered as an approximation of the total gas-dynamic work, performed during a complete breathing cycle.
Most importantly, this kind of modelling has been shown to be predictive for a large age range from childhood to adulthood.35 In fact, the healthy human body has a wide range of regulatory mechanisms during normal breathing and can serve as a model to understand what the interactions would look like in patients with respiratory disorders. The pattern of breathing and airway resistance during exercise in terms of the relationships between inspiratory time (TI), tidal volume (VT) and EELV has been studied in detail by Hesser and Lind,48–50 showing the interrelationship between TI and VT at different ranges. This is important for assessing the overall understanding of how airway dynamics relate to the distending forces of the thoraco-pulmonary system, especially in diseased subjects with pulmonary hyperinflation, small airway dysfunction and/or pulmonary restriction. Apart from the advantage that airway dynamics can be assessed in close relation to these promoting factors of actual breathing, plethysmographic measurements offer the advantage that they can be performed during tidal breathing, requiring little cooperation from the subject and, therefore are effort independent. For such measurements, deep inspiration and forced breathing manoeuvres that influence the regional distribution of the air are not required, and such side effects can be avoided.
Impact of the ageing pulmonary system on airway dynamics
Ageing is associated with the loss of lung elastic recoil and stiffening of the chest wall as well as decreased maximum respiratory pressure-generating capacity, airway calibre and expiratory flow rates during exercise.51–54 The mechanisms responsible for the elevated sWOB with age can be better understood, if sWOB is partitioned into the inspiratory (sWOBin) and expiratory (sWOBex) part, related to age and other linked parameters. In fact, as shown in figure 2 both sWOBin and sWOBex significantly increase with age curvilinearly (F=16.7; p<0.001), and additionally, sWOBex increases significantly more than sWOBin (F=378.9; p<0.001). This finding confirms previous results obtained in exercise studies, that the smaller airways and greater mechanical constraints during exercise likely result in increased aerodynamic sWOB in the older compared with the younger adults.54 It is well documented that in normal subjects at rest, sWOBin and sReff
IN and hence the work needed against lung and chest wall inspiratory resistance is a minor component of the work of breathing.55 The effective resistance of the relaxed chest wall is caused by pressure–volume hysteresis measured as sReff
IN. However, sReff
IN is small at normal breathing rates,56 the diameter of the bronchi enlarges during inspiration and consequently sWOBin is lower than sWOBex. As the regression analyses indicate, there are two other mechanisms, which must be considered. The ratio between VT and FRCpleth (ventilation in relation to the EELV) decreases dramatically in young age, remaining thereafter more or less stable. This parameter could play an important role in patients with obstructive lung disease, if the EELV is increased due to pulmonary hyperinflation, or trapped gases are present.
Relevance to differentiate parameters of the inspiratory and expiratory parts separately
As it could be shown by the canonical discriminant analysis and based on Wilks’ lambda (Λ) test statistics, sRtot presented with the most discriminative power followed by sWOBex, sReff, sWOBin, sReff
IN and sReff
EX differentiating between the three diagnostic classes. Noteworthy, the three spirometric parameters FEV1, FEV1/FVC and FEF25–75 were excluded from the model. Furthermore, the rating list of discriminative lung function parameters revealed that the inclusion of aerodynamic parameters separating the inspiratory from the expiratory limb of the sRaw-loop is highly recommended.
Limits of the methods
In modern plethysmographs, the thermos-hygrometric artefact from inspiration to expiration is automatically corrected by algorithms however, different depending on the manufacturers. It is understandable that the details of these algorithms are not published or provided with the manuals of the plethysmograph. Therefore, it was essential to have in each centre the same plethysmograph and the same software. It follows that the reference equations are valid only for the Jaeger plethysmograph used to collect these data.
Perspectives and clinical implications
We have recently demonstrated that parameters of airway dynamics are important diagnostic tools as target parameters both, the assessment of the bronchodilator response39 and the assessment of airway hyper-reactivity by methacholine challenge test in patients with asthma, ACO and COPD.57 Both test techniques are principally based on defining airway patency, and hence changes of airway dynamics during these test procedures. In so far, the specific aerodynamic work of breathing could well be a new reliable parameter to define specific disease endophenotypes.
The availability of normative reference equations applied over a wide age range are prerequisites for studies predicting disease progression in obstructive lung diseases. Not only spirometric parameters but also plethysmographic parameters of airway dynamics evaluated from the sRaw-loop feature new insights into the physiopathology of these diseases. There is increasing interest in incorporating independent discriminatory parameters within new concepts of ‘artificial intelligence’,4 58 highlighting and comparing the various functional facets and the physiological complexity within obstructive lung diseases. Therefore, using extended sets of spirometric and plethysmographic parameters in a multivariate approach, can enable the identification of functional traits within the diagnosis of obstructive pulmonary diseases. A new option now is to use these normative equations for target parameters to differentiate the functional physiopathology between different airway diseases. Preliminary results of an ongoing study reveal that, if a whole set of holistically evaluated parameters of spirometry and plethysmography are well-tailored and introduced within a multidimensional perception, treatable trait strategies as new concepts towards precision medicine can be developed.7 10 It follows that the analysis of new parameters obtained by the plethysmographic sRaw-loop may well discriminate between different obstructive lung diseases and their subtypes.