Early Detection of Asthma via Enhanced Resolution of Small Airways Using Ultra-Low Frequency Impulse Oscillometry

Examination of lung function for diagnosis and monitoring of diseases such as chronic obstructive pulmonary disease (COPD) and asthma can be performed with a variety of pulmonary function testing (PFT) techniques. The most commonly prescribed of these procedures are spirometry and whole-body plethysmography. However, these active participation tests depend on forced breathing maneuvers, may be physically exhausting, might not produce enough information, and are susceptible to being subject-dependent. In contrast, passive PFT approaches such as the forced oscillation technique (FOT) and the impulse oscillometry system (IOS) are increasingly being utilized for measuring lung mechanics because they require only minimal participation, which is a crucial advantage when dealing with very young pediatric patients, geriatric patients, and those with cognitive impairments or who are unconscious. Using external pressure oscillations superimposed onto tidal breathing, both FOT and IOS reveal intricate details behind breathing mechanics by measuring the frequency response of the respiratory system from the composite test signals to determine input impedance at the airway opening and detect lung obstructions and restrictions. IOS features a unique discriminative property to identify the location of lung obstruction, which makes IOS very valuable for the detection and diagnosis of small airways disease (SAD), also known as small airways impairment (SAI), and impending asthma potentially long before their clinical manifestation. However, IOS measurements are coarse and there is also a need for studies with test functions in the low frequency range to determine the respiratory impedance of distant airways. Furthermore, particularly for preschoolers, current limitations of IOS include the lack of an international test standard; a lack of reference equations, parameter values, and identifiable SAD biomarkers; and a high probability of impedance distortion and biased estimations due to signal interference from spontaneous breathing at low frequencies or upper airway shunting effects at high frequencies. This Dissertation aims at an enhanced IOS determination of the function of small airways via analysis of their frequency response to facilitate early SAD detection, which is considered a phenotype and likely childhood precursor for the pathogenesis of asthma. The ultimate goal of this research is to aid diagnosis and monitoring of asthma at an early stage, to treat and control the disease, and improve the quality of life of asthmatic individuals, particularly pediatric patients. This research introduces the development of a novel electrical model of the respiratory system to determine the mechanical impedance of peripheral airways using IOS-based data in the range from 5 Hz down to tidal breathing frequency, the ultra-low frequency range (ULF). The presented approach models the effects of noninvasive application of ULF excitation signals into the respiratory system to parameterize its frequency response below 5 Hz and ascertain sharper resolution of 7th to 19th generation airways