On the respiratory mechanics measured by forced oscillation technique in patients with systemic sclerosis

Abstract

Background: Pulmonary complications are the most common cause of death and morbidity in systemic sclerosis (SSc). The forced oscillation technique (FOT) offers a simple and detailed approach to investigate the mechanical properties of the respiratory system. We hypothesized that SSc may introduce changes in the resistive and reactive properties of the respiratory system, and that FOT may help the diagnosis of these abnormalities.

Methodology/principal findings: We tested these hypotheses in controls (n = 30) and patients with abnormalities classified using spirometry (n = 52) and pulmonary volumes (n = 29). Resistive data were interpreted with the zero-intercept resistance (Ri) and the slope of the resistance (S) as a function of frequency. Reactance changes were evaluated by the mean reactance between 4 and 32 Hz (Xm) and the dynamic compliance (Crs,dyn). The mechanical load was evaluated using the absolute value of the impedance in 4 Hz (Z4Hz). A compartmental model was used to obtain central (R) and peripheral (Rp) resistances, and alveolar compliance (C). The clinical usefulness was evaluated by investigating the area under the receiver operating characteristic curve (AUC). The presence of expiratory flow limitation (EFL) was also evaluated. For the groups classified using spirometry, SSc resulted in increased values in Ri, R, Rp and Z4Hz (p<0.003) and reductions in Crs,dyn, C and Xm (p<0.004). Z4Hz, C and Crs,dyn exhibited a high diagnostic accuracy (AUC>0.90). In groups classified by pulmonary volume, SSc resulted in reductions in S, Xm, C and Crs,dyn (p<0.01). Xm, C and Crs,dyn exhibited adequate diagnostic accuracy (AUC>0.80). It was also observed that EFL is not common in patients with SSc.

Conclusions/significance: This study provides evidence that the respiratory resistance and reactance are changed in SSc. This analysis provides a useful description that is of particular significance for understanding respiratory pathophysiology and to ease the diagnosis of respiratory abnormalities in these patients.

Figure 1. Electrical representation of the two-compartment model used to analyze respiratory impedance.

Resistance (R), inductance (I) and capacitance (C) are the analogs of mechanical resistance, inertance and compliance, respectively. This model contributes to gain additional insight into anatomical or pathophysiological changes in the studied subjects allowing the evaluation of central (R) and peripheral (Rp) airway resistance.

Figure 2. Comparison of the resistive parameters obtained from groups of patients classified according to the spirometric exams.

Analyses using the forced oscillations technique showed that the total resistance of the respiratory system (Ri; Figure A) and the mean resistance (Rm; Figure B) increased in the individuals with restrictive disorder based on the spirometric test and in the patients classified as normal. The restriction resulted in more negative S values, which denote the presence of non-homogeneities in the respiratory system of these patients (Figure C). The top and the bottom of the box plot represent the 25^th- to 75^th-percentile values, while the circle represents the mean value, and the bar across the box represents the 50^th-percentile value. The whiskers outside the box represent the 10^th- to 90^th-percentile values.

Figure 3. Influence of the pattern classified as restrictive in the spirometric exams on the reactive properties of the respiratory system.

Mean reactance (Xm; Figure A) and the dynamic compliance of the respiratory system (Crs,dyn; Figure B) decreased, whereas the resonant frequency (fr; Figure C) and the impedance modulus at 4 Hz (Z4Hz; Figure D) exhibited significant increases. Notably, there are significant alterations in Crs,dyn and Z4Hz even in the patients classified as normal (Figures C and D).

Figure 4. Influence of the pattern classified as restrictive in the spirometric exams on parameter values estimated from the model described in Figure 1.

The increasing restriction was accompanied by a correspondent gradual elevation of central (A) and peripheral (B) resistance values. These changes are significant even in patients with normal spirometry. Respiratory inertance (C) increased in SSc. The changes observed in resistance and inertance may be explained by reductions in the radius of the airways. As can be observed in (D), SSc also resulted in reduced values of compliance.

Figure 5. Effect of the restricted pattern in the lung volume tests on the resistive properties of the respiratory system.

The total resistance of the respiratory system (Ri; Figure A) and the mean resistance (Rm; Figure B) did not change, whereas in (C), we observe that the restriction results in more negative S values.

Figure 6. Influence of the restricted pattern in the lung volume tests on the reactive properties of the respiratory system.

The mean reactance (Xm; Figure A) and the dynamic compliance of the respiratory system (Crs,dyn; Figure B) decreased, whereas the resonant frequency (fr; Figure C) and the impedance modulus at 4 Hz (Z4Hz; Figure D) exhibited a significant increase.

Figure 7. Influence of the restricted pattern in the lung volume tests on parameter values estimated from the model described in Figure 1.

Changes in central (A) and peripheral resistance (B), as well as in I (C) values were non-significant. Compliance was significantly reduced in restrictive patients (D).

Figure 8. Expiratory flow limitation (EFL) index in patients with systemic sclerosis. EFL events are described by values above the threshold value plotted as a horizontal line.

None of the 411 breaths cycles analyzed in the eighteen studied subjects had expiratory flow limitation as defined by an EFLi > 2.8 cmH₂O/L/s. These results provide evidence that EFL during spontaneous breathing is not common in patients with SSc.