Alessandro Gobbi

Mechanical effects of obesity on airway responsiveness in otherwise healthy humans.

We investigated whether obesity is associated with airway hyperresponsiveness in otherwise healthy humans and, if so, whether this correlates with a restrictive lung function pattern or a decreased number of sighs at rest and/or during walking. Lung function was studied before and after inhaling methacholine (MCh) in 41 healthy subjects with body mass index ranging from 20 to 56. Breathing pattern was assessed during a 60-min rest period and a 30-min walk. The dose of MCh that produced a 50% decrease in the maximum expiratory flow measured in a body plethysmograph (PD50MCh) was inversely correlated with body mass index (r2=0.32, P<0.001) and waist circumference (r2=0.25, P<0.001). Significant correlations with body mass index were also found with the maximum changes in respiratory resistance (r2=0.19, P<0.001) and reactance (r2=0.40, P<0.001) measured at 5 Hz. PD50MCh was also positively correlated with functional residual capacity (r2=0.56, P<0.001) and total lung capacity (r2=0.59, P<0.001) in men, but not in women. Neither PD50MCh nor body mass index correlated with number of sighs, average tidal volume, ventilation, or breathing frequency. In this study, airway hyperresponsiveness was significantly associated with obesity in otherwise healthy subjects. In obese men, but not in women, airway hyperresponsiveness was associated with the decreases in lung volumes.

Home monitoring of within-breath respiratory mechanics by a simple and automatic forced oscillation technique device

Spirometry is the gold standard to determine the presence of airflow obstruction, but it requires volitional participation and needs qualified supervision. The forced oscillation technique (FOT) measures respiratory input impedance (Zrs) during spontaneous breathing and it could be useful for unsupervised monitoring of airway obstruction. We developed a FOT device for home monitoring of Zrs which transmits the data through the Internet. Its accuracy, stability and reliability were evaluated in a pilot study measuring the Zrs in the unsupervised self-measurements of five healthy subjects. Finally, to explore the applicability of the concept, 36 consecutive daily home measurements were recorded from one healthy subject and one chronic obstructive pulmonary disease (COPD) patient. The accuracy of the device fulfilled FOT guidelines, and the reliability test showed a mean discrepancy of resistance of 0.10 +/- 0.01 cmH(2)O s L(-1). The data from the healthy subjects demonstrated high repeatability in assessing Zrs. The measurements on the healthy subjects and the patient with COPD suggest the feasibility of unsupervised FOT measurements. The healthy subjects showed minimal daily variations in Zrs, whereas the patient with COPD had large differences in mean values and important fluctuations over day-to-day measurements. The results of the pilot study demonstrate that unsupervised home monitoring of Zrs using the FOT yields accurate and reproducible data. It could provide new insights into the dynamics of airway obstruction and improve the understanding and management of obstructive diseases.

Ventilation heterogeneity in obesity

Obesity is associated with important decrements in lung volumes. Despite this, ventilation remains normally or near normally distributed at least for moderate decrements in functional residual capacity (FRC). We tested the hypothesis that this is because maximum flow increases presumably as a result of an increased lung elastic recoil. Forced expiratory flows corrected for thoracic gas compression volume, lung volumes, and forced oscillation technique at 5-11-19 Hz were measured in 133 healthy subjects with a body mass index (BMI) ranging from 18 to 50 kg/m(2). Short-term temporal variability of ventilation heterogeneity was estimated from the interquartile range of the frequency distribution of the difference in inspiratory resistance between 5 and 19 Hz (R5-19_IQR). FRC % predicted negatively correlated with BMI (r = -0.72, P < 0.001) and with an increase in slope of either maximal (r = -0.34, P < 0.01) or partial flow-volume curves (r = -0.30, P < 0.01). Together with a slight decrease in residual volume, this suggests an increased lung elastic recoil. Regression analysis of R5-19_IQR against FRC % predicted and expiratory reserve volume (ERV) yielded significantly higher correlation coefficients by nonlinear than linear fitting models (r(2) = 0.40 vs. 0.30 for FRC % predicted and r(2) = 0.28 vs. 0.19 for ERV). In conclusion, temporal variability of ventilation heterogeneities increases in obesity only when FRC falls approximately below 65% of predicted or ERV below 0.6 liters. Above these thresholds distribution is quite well preserved presumably as a result of an increase in lung recoil.

Short-term variability in respiratory impedance and effect of deep breath in asthmatic and healthy subjects with airway smooth muscle activation and unloading

Inspiratory resistance (RINSP) and reactance (XINSP) were measured for 7 min at 5 Hz in 10 subjects with mild asymptomatic asthma and 9 healthy subjects to assess the effects of airway smooth muscle (ASM) activation by methacholine (MCh) and unloading by chest wall strapping (CWS) on the variability of lung function and the effects of deep inspiration (DI). Subjects were studied at control conditions, after MCh, with CWS, and after MCh with CWS. In all experimental conditions XINSP was significantly more negative in subjects with asthma than in healthy subjects, suggesting greater inhomogeneity in the former. However, the variability in both RINSP and XINSP was increased by either ASM activation or CWS, without significant difference between groups. DI significantly reversed MCh-induced changes in RINSP both in subjects with asthma and healthy subjects, but XINSP in the former only. This effect was impaired by CWS more in subjects with asthma than in healthy subjects. The velocity of RINSP and XINSP recovery after DI was faster in subjects with asthma than healthy subjects. In conclusion, these results support the opinion that the short-term variability in respiratory impedance is related to ASM tone or operating length, rather than to the disease. Nevertheless, ASM in individuals with asthma differs from that in healthy individuals in an increased velocity of shortening and a reduced sensitivity to mechanical stress when strain is reduced.

A Novel Simple Internet-Based System for Real Time Monitoring and Optimizing Home Mechanical Ventilation

The dissemination of the available telemedicine systems for the optimization of home mechanical ventilation (HMV) is prevented by the need of complex infrastructures. We developed a device which, once connected to Internet through the mobile phone network, allows an authorized physician connected to Internet to monitor the ventilator signals and modify the settings in real-time without the need of external data servers. The system was evaluated during experiments performed by tele-controlling a mechanical ventilator in Barcelona from Milano. A bench study verified the reliability and robustness of the system while an in-vivo test showed that it was possible to monitor and tele-control the ventilator to maintain the oxygen saturation of a rat ventilated in Barcelona subjected to interventions. Given that the system avoids the need for any complex telemedicine architecture and allows an individual and independent ventilator tele-control, it can be a new helpful tool to optimize HMV.

Severity grading of chronic obstructive pulmonary disease: the confounding effect of phenotype and thoracic gas compression

Current guidelines recommend severity of chronic obstructive pulmonary disease be graded by using forced expiratory volume in 1 s (FEV1). But this measurement is biased by thoracic gas compression depending on lung volume and airflow resistance. The aim of this study was to test the hypothesis that the effect of thoracic gas compression on FEV1 is greater in emphysema than chronic bronchitis because of larger lung volumes, and this influences severity classification and prognosis. FEV1 was simultaneously measured by spirometry and body plethysmography (FEV1-pl) in 47 subjects with dominant emphysema and 51 with dominant chronic bronchitis. Subjects with dominant emphysema had larger lung volumes, lower diffusion capacity, and lower FEV1 than those with dominant chronic bronchitis. However, FEV1-pl, patient-centered variables (dyspnea, quality of life, exercise tolerance, exacerbation frequency), arterial blood gases, and respiratory impedance were not significantly different between groups. Using FEV1-pl instead of FEV1 shifted severity distribution toward less severe classes in dominant emphysema more than chronic bronchitis. The body mass, obstruction, dyspnea, and exercise (BODE) index was significantly higher in dominant emphysema than chronic bronchitis, but this difference significantly decreased when FEV1-pl was substituted for FEV1. In conclusion, the FEV1 is biased by thoracic gas compression more in subjects with dominant emphysema than in those with chronic bronchitis. This variably and significantly affects the severity grading systems currently recommended.

Mechanical correlates of dyspnea in bronchial asthma

We hypothesized that dyspnea and its descriptors, that is, chest tightness, inspiratory effort, unrewarded inspiration, and expiratory difficulty in asthma reflect different mechanisms of airflow obstruction and their perception varies with the severity of bronchoconstriction. Eighty‐three asthmatics were studied before and after inhalation of methacholine doses decreasing the 1‐sec forced expiratory volume by ~15% (mild bronchoconstriction) and ~25% (moderate bronchoconstriction). Symptoms were examined as a function of changes in lung mechanics. Dyspnea increased with the severity of obstruction, mostly because of inspiratory effort and chest tightness. At mild bronchoconstriction, multivariate analysis showed that dyspnea was related to the increase in inspiratory resistance at 5 Hz (R5) (r2 = 0.10, P = 0.004), chest tightness to the decrease in maximal flow at 40% of control forced vital capacity, and the increase in R5 at full lung inflation (r2 = 0.15, P = 0.006), inspiratory effort to the temporal variability in R5‐19 (r2 = 0.13, P = 0.003), and unrewarded inspiration to the recovery of R5 after deep breath (r2 = 0.07, P = 0.01). At moderate bronchoconstriction, multivariate analysis showed that dyspnea and inspiratory effort were related to the increase in temporal variability in inspiratory reactance at 5 Hz (X5) (r2 = 0.12, P = 0.04 and r2 = 0.18, P < 0.001, respectively), and unrewarded inspiration to the decrease in X5 at maximum lung inflation (r2 = 0.07, P = 0.04). We conclude that symptom perception is partly explained by indexes of airway narrowing and loss of bronchodilatation with deep breath at low levels of bronchoconstriction, but by markers of ventilation heterogeneity and lung volume recruitment when bronchoconstriction becomes more severe.

Toward Predicting Individual Risk in Asthma Using Daily Home Monitoring of Resistance

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