In vitro-in vivocorrelation of aerosol deposition before and after metered-dose inhaler coaching in healthy children.

Although pressurized metered dose inhaler (pMDI) education is a routine part of childhood asthma management and encouraging 'optimal breathing patterns' (i.e. slowly, deeply, completely, and with a mouth seal on the mouthpiece) is an integral part of recommended pMDI education, there is currently no quantifiable way to determine if a child is inhaling their medication correctly or optimally through a valved holding chamber (VHC). The TipsHaler™ (tVHC) is a prototype VHC device that measures inspiratory time, flow, and volume without changing the properties of the medication aerosol. The measurementsin vivorecorded by the tVHC can be downloaded and transferred to a spontaneous breathing lung model to simulate the inhalational patternsin vitroand also determine the deposition of inhaled aerosol mass with each pattern. We hypothesized that pediatric patients' inhalational patterns when using a pMDI would improve after active coaching via tVHC. This would increase the pulmonary deposition of inhaled aerosols in anin vitromodel. To test this hypothesis, we conducted a single-site, prospective, pilot, pre-and-post intervention study paired with a bedside-to-bench experiment. Healthy, inhaler-naïve subjects used a placebo inhaler in conjunction with the tVHC before and after coaching and recorded inspiratory parameters. These recordings were then implemented into a spontaneous breathing lung model during albuterol MDI delivery, and pulmonary deposition of albuterol was quantified. In this pilot study, active coaching resulted in a statistically significant increase in inspiratory time (n= 8,p= 0.0344, 95%CI: 0.082 to ∞). tVHC recorded inspiratory parameters obtained from patients were successfully implemented in thein vitromodel, which demonstrated that both inspiratory time (n= 8,r= 0.78,p <0.001, 95%CI: 0.47-0.92) and volume (n= 8,r= 0.58,p =0.0186, 95%CI: 0.15-0.85) strongly correlate with pulmonary deposition of inhaled drugs.

Oscillation Mechanics, Integer and Fractional Respiratory Modeling in COPD: Effect of Obstruction Severity.

Purpose: This research examines the emerging role of respiratory oscillometry associated with integer (InOr) and fractional order (FrOr) respiratory models in the context of groups of patients with increasing severity. The contributions to our understanding of the respiratory abnormalities along the course of increasing COPD severity and the diagnostic use of this method were also evaluated. Patients and Methods: Forty-five individuals with no history of smoking or pulmonary diseases (control group) and 141 individuals with diagnoses of COPD were studied, being classified into 45 mild, 42 moderate, 36 severe and 18 very severe cases. Results: This study has shown initially that the course of increasing COPD severity was adequately described by the model parameters. This resulted in significant and consistent correlations among these parameters and spirometric indexes. Additionally, this evaluation enhanced our understanding of the respiratory abnormalities in different COPD stages. The diagnostic accuracy analyses provided evidence that hysteresivity, obtained from FrOr modeling, allowed a highly accurate identification in patients with mild changes [area under the receiver operator characteristic curve (AUC)= 0.902]. Similar analyses in groups of moderate and severe patients showed that peripheral resistance, derived from InOr modeling, provided the most accurate parameter (AUC=0.898 and 0.998, respectively), while in very severe patients, traditional, InOr and FrOr parameters were able to reach high diagnostic accuracy (AUC>0.9). Conclusion: InOr and FrOr modeling improved our knowledge of the respiratory abnormalities along the course of increasing COPD severity. In addition, the present study provides evidence that these models may contribute in the diagnosis of COPD. Respiratory oscillometry exams require only tidal breathing and are easy to perform. Taken together, these practical considerations and the results of the present study suggest that respiratory oscillometry associated with InOr and FrOr models may help to improve lung function tests in COPD.

Association of respiratory integer and fractional-order models with structural abnormalities in silicosis.

BACKGROUND AND OBJECTIVE: Integer and fractional-order models have emerged as powerful methods for obtaining information regarding the anatomical or pathophysiological changes that occur during respiratory diseases. However, the precise interpretation of the model parameters in light of the lung structural changes is not known. This study analyzed the associations of the integer and fractional-order models with structural changes obtained using multidetector computed tomography densitometry (MDCT) and pulmonary function analysis. METHODS: Integer and fractional-order models were adjusted to data obtained using the forced oscillation technique (FOT). The results obtained in controls (n = 20) were compared with those obtained in patients with silicosis (n = 32), who were submitted to spirometry, body plethysmograph, FOT, diffusing capacity of the lungs for carbon monoxide (DLCO), and MDCT. The diagnostic accuracy was also investigated using ROC analysis. RESULTS: The observed changes in the integer and fractional-order models were consistent with the pathophysiology of silicosis. The integer-order model showed association only between inertance and the non-aerated compartment (R = -0.69). This parameter also presented the highest associations with spirometry (R = 0.81), plethysmography (-0.61) and pulmonary diffusion (R = 0.53). Considering the fractional-order model, the increase in the poorly aerated and non-aerated regions presented direct correlations with the fractional inertance (R = 0.48), respiratory damping (R = 0.37) and hysteresivity (R = 0.54) and inverse associations with its fractional exponent (R = -0.62) and elastance (-0.35). Significant associations were also observed with spirometry (R = 0.63), plethysmography (0.37) and pulmonary diffusion (R = 0.51). Receiver operator characteristic analysis showed a higher accuracy in the FrOr model (0.908) than the eRIC model (0.789). CONCLUSIONS: Our study has shown clear associations of the integer and fractional-order parameters with anatomical changes obtained via MDCT and pulmonary function measurements. These findings help to elucidate the physiological interpretation of the integer and fractional-order parameters and provide evidence that these parameters are reflective of the abnormal changes in silicosis. We also observed that the fractional-order model showed smaller curve-fitting errors, which resulted in a higher diagnostic accuracy than that of the eRIC model. Taken together, these results provide strong motivation for further studies exploring the clinical and scientific use of these models in respiratory medicine.

Forced oscillation technique for early detection of the effects of smoking and COPD: contribution of fractional-order modeling.

PURPOSE: The aim of the present study was to evaluate the performance of the forced oscillation technique (FOT) for the early diagnosis of the effects of smoking and COPD. The contributions of the integer-order (InOr) and fractional-order (FrOr) models were also evaluated. PATIENTS AND METHODS: In total, 120 subjects were analyzed: 40 controls, 40 smokers (20.3±9.3 pack-years) and 40 patients with mild COPD. RESULTS: Initially, it was observed that traditional FOT parameters and the InOr and FrOr models provided a consistent description of the COPD pathophysiology. Mild COPD introduced significant increases in the FrOr inertance, damping factor and hysteresivity (P<0.0001). These parameters were significantly correlated with the spirometric parameters of central and small airway obstruction (P<0.0001). The diagnostic accuracy analyses indicated that FOT parameters and InOr modeling may adequately identify these changes (area under the receiver operating characteristic curve - AUC >0.8). The use of FrOr modeling significantly improved this process (P<0.05), allowing the early diagnosis of smokers and patients with mild COPD with high accuracy (AUC >0.9). CONCLUSION: FrOr modeling improves our knowledge of modifications that occur in the early stages of COPD. Additionally, the findings of the present study provide evidence that these models may play an important role in the early diagnosis of COPD, which is crucial for improving the clinical management of the disease.

A Review on Human Respiratory Modeling.

Input impedance of the respiratory system is measured by forced oscillation technique (FOT). Multiple prior studies have attempted to match the electromechanical models of the respiratory system to impedance data. Since the mechanical behavior of airways and the respiratory system as a whole are similar to an electrical circuit in a combination of series and parallel formats some theories were introduced according to this issue. It should be noted that, the number of elements used in these models might be less than those required due to the complexity of the pulmonary-chest wall anatomy. Various respiratory models have been proposed based on this idea in order to demonstrate and assess the different parts of respiratory system related to children and adults data. With regard to our knowledge, some of famous respiratory models in related to obstructive, restrictive diseases and also Acute Respiratory Distress Syndrome (ARDS) are reviewed in this article.