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Spirometry revisited
Boek - Dissertatie
Ondertitel:expanding the clinical potential of peak inspiratory flow
Spirometry is a widely used and accessible lung function test consisting of at least three forced inspiratory/expiratory manoeuvres. Due to the effort-dependency of the inspiratory portion of the flow-volume loop, quantitative interpretation of spirometry indices has long been limited to the expiratory portion of the flow-volume loop. Recent guidelines, however, have emphasised the importance of both inspiratory and expiratory parts of spirometry where the inspiratory part serves as a quality criterion for the spirometric manoeuvre. With an aim to actually use the inspiratory peak flow (PIFspiro), we performed a study in 187 healthy Caucasian adults evenly distributed across age decades 20-80 years. We were able to obtain reliable PIFspiro values with good between-manoeuvre repeatability. Based on these results we constructed reference equations for PIFspiro using the state of the art Generalised Additive Models for Location, Scale and Shape (GAMLSS) statistical method which allows predicted values and limits of normal to depend on age and height. In healthy subjects, these PIFspiro measurements were feasible and required on average 3 inspiratory spirometries which corresponds to the typical number of spirometries in clinical practice. As such, inspiratory spirometry evolved from being merely a quality criterion for expiratory spirometry and a qualitative lung function test, to a proper measure. This new quantitative approach (paper 1) to maximal inspiratory flow rates expands the potential for clinical use of the spirometry curve, beyond the common interpretation of fixed ratios or flow-volume loop contours.
Many patients with obstructive lung disease receive inhaled drug formulation by means of a dry powder inhaler (DPI) device that requires sufficient peak inspiratory flow over its internal resistance (PIFR) to generate a respirable drug particle fraction. We described the existing clinical gaps with inhaler therapy and inhaler choice in paper 2.
We then explored the clinical potential of PIFspiro in asthma and COPD (paper 3), hypothesising that it could be used to predict PIFR for an individual patient, since PIFR is such a critical determinant of successful dry powder inhaler use. We first verified that in people living with asthma and COPD, reliable PIFspiro measurements could be obtained, showing similar feasibility as that observed in healthy subjects, namely requiring only 3 in- and expiratory spirometry manoeuvres. We then designed a model to predict PIFR over any given device resistance, solely based on PIFspiro (which inherently incorporates patient characteristics such as height, sex and age), and on an inhalation device characteristic which reflects the DPI's internal resistance. The model proved valid, since the predicted PIFR values for the different device resistances were not significantly different from the actually measured PIFR values over the corresponding simulated device resistances in a 'validation' patient subgroup. In this way, we turned PIFspiro measurement into a novel tool to guide dry powder inhaler choice, such that clinicians can estimate a patient's PIFR over any DPI device, based solely on a good quality inspiratory and expiratory spirometry.
In the last study included in his dissertation, the clinical potential of PIFspiro is expanded by applying PIFspiro measurement methodology to patients with different neuromuscular diseases. As was the case in healthy subjects, asthma and COPD, reliable PIFspiro values were also obtained here, in on average 3 inspiratory spirometry manoeuvres. Until date, inspiratory muscle function is assessed non invasively with an additional measurement of maximal inspiratory pressure (MIP) on top of spirometry. Based on the adult reference values obtained in our first study, we expressed individual PIFspiro values as z-scores and explored the ability of PIFspiro z-score to predict MIP below the lower limit of normal, to screen for inspiratory muscle weakness. We were able to identify two clinically useful PIFspiro z-score cut-offs that predict abnormal MIP: a PIFspiro z-score of -2.37 that yields the best combination of sensitivity and specificity, and a PIFspiro z-score of -1.65 that maximises sensitivity, which is appropriate for a screening test. Coincidentally, the -1.65 PIFspiro z-score cut-off corresponds to a widely used lower limit of normal, which facilitates it clinical applicability.
The results of our 3 studies show how a routine spirometry can offer additional information applicable in health and disease, further exploring and exploiting the neglected part of the flow-volume loop.
Many patients with obstructive lung disease receive inhaled drug formulation by means of a dry powder inhaler (DPI) device that requires sufficient peak inspiratory flow over its internal resistance (PIFR) to generate a respirable drug particle fraction. We described the existing clinical gaps with inhaler therapy and inhaler choice in paper 2.
We then explored the clinical potential of PIFspiro in asthma and COPD (paper 3), hypothesising that it could be used to predict PIFR for an individual patient, since PIFR is such a critical determinant of successful dry powder inhaler use. We first verified that in people living with asthma and COPD, reliable PIFspiro measurements could be obtained, showing similar feasibility as that observed in healthy subjects, namely requiring only 3 in- and expiratory spirometry manoeuvres. We then designed a model to predict PIFR over any given device resistance, solely based on PIFspiro (which inherently incorporates patient characteristics such as height, sex and age), and on an inhalation device characteristic which reflects the DPI's internal resistance. The model proved valid, since the predicted PIFR values for the different device resistances were not significantly different from the actually measured PIFR values over the corresponding simulated device resistances in a 'validation' patient subgroup. In this way, we turned PIFspiro measurement into a novel tool to guide dry powder inhaler choice, such that clinicians can estimate a patient's PIFR over any DPI device, based solely on a good quality inspiratory and expiratory spirometry.
In the last study included in his dissertation, the clinical potential of PIFspiro is expanded by applying PIFspiro measurement methodology to patients with different neuromuscular diseases. As was the case in healthy subjects, asthma and COPD, reliable PIFspiro values were also obtained here, in on average 3 inspiratory spirometry manoeuvres. Until date, inspiratory muscle function is assessed non invasively with an additional measurement of maximal inspiratory pressure (MIP) on top of spirometry. Based on the adult reference values obtained in our first study, we expressed individual PIFspiro values as z-scores and explored the ability of PIFspiro z-score to predict MIP below the lower limit of normal, to screen for inspiratory muscle weakness. We were able to identify two clinically useful PIFspiro z-score cut-offs that predict abnormal MIP: a PIFspiro z-score of -2.37 that yields the best combination of sensitivity and specificity, and a PIFspiro z-score of -1.65 that maximises sensitivity, which is appropriate for a screening test. Coincidentally, the -1.65 PIFspiro z-score cut-off corresponds to a widely used lower limit of normal, which facilitates it clinical applicability.
The results of our 3 studies show how a routine spirometry can offer additional information applicable in health and disease, further exploring and exploiting the neglected part of the flow-volume loop.
Aantal pagina's: 145
Jaar van publicatie:2023
Trefwoorden:Spirometry, lung function test
Toegankelijkheid:Embargoed