Altered airway mechanics in the context of obesity and asthma

Abstract

The obesity epidemic is causing a rise in asthma incidence due to the appearance of an obesity-specific late-onset nonallergic (LONA) phenotype. We investigated why only a subset of obese participants develop LONA asthma by determining how obesity, both alone and in combination with LONA asthma, affects the volume dependence of respiratory system impedance. We also determined how obesity and asthma affect impedance during and following challenge with the PC₂₀ dose of methacholine. We found during passive exhalation that all obese participants, in contrast to lean controls and lean asthmatics, experienced similarly profound elevations in lung elastance as they approached functional residual capacity. We also found, however, that the LONA asthmatics had a greater negative dependence of airway resistance on lung volume over the middle of the volume range compared with the other groups. Methacholine challenge with the PC₂₀ dose led to comparable changes in respiratory system impedance in the four study groups, but the doses themselves were substantially lower in both obese and lean asthmatic participants compared with obese and lean controls. Also, the obese LONA asthmatics had higher breathing frequencies and lower tidal volumes postchallenge compared with the other participants. Taken together, these results suggest that all obese individuals experience substantial lung collapse as they approach functional residual capacity, presumably due to the weight of the chest wall. It remains unclear why obese LONA asthmatics are hyperresponsive to methacholine while obese nonasthmatic individuals are not.NEW & NOTEWORTHY Why only a subset of severely obese subjects develop late-onset nonallergic (LONA) asthma remains unknown, although it is widely assumed that compression of the lungs by the chest wall is somehow involved. We show that lung compression is common to obese individuals both without asthma and with LONA asthma but that those with LONA asthma may have increased airway wall compliance and possibly also a reduced ability to recruit collapsed lung.

Keywords: airway resistance; airway wall compliance; mathematical model; respiratory system impedance.

Fig 1.

An example of real and imaginary parts of impedance [R(f) (closed circles) and X(f) (open circles)] together with the fits provided by the 2-compartment model. The areas A_X and A_R are shown as the shaded regions. The diagram at right shows the 2-compartment series model of the respiratory system characterized by the 5 parameters central airway resistance (R_c), central airway elastance (E_c), central airway gas inertance (I_c), peripheral airway resistance (R_p), and peripheral airway elastance (E_p).

Fig 2.

Respiratory system resistance (R_rs) during slow relaxed expiration from total lung capacity (1.0) to functional residual capacity (0.0). The data are presented as means ± SE.

Fig. 3.

Respiratory system resistance (R_rs) versus fraction of lung volume between functional residual capacity (FRC) (0) and total lung capacity (TLC) (1.0). The symbols are mean values for each of the study groups between 20% and 80% of the volume range. Symbols represent the experimental measurements; solid lines are linear fits to each group. Linear regression analysis was used to determine that all slopes are significantly different (P < 0.05, Table 2).

Fig 4.

Respiratory system elastance (E_rs) during slow relaxed expiration from total lung capacity (1.0) to functional residual capacity (0.0). The data are presented as means ± SE. We therefore determined the slopes of linear fits to E_rs versus normalized volume over the lower 20% of the volume range, with the exception of the last point (volume of 0). These slopes of mean $E_{rs}$ over the lower 20% of the volume range were determined by linear regression. The slopes for the 2 obese groups are significantly greater in magnitude compared with those of the 2 lean groups as assessed by the fact that their respective ± SE ranges do not overlap. LONA, late-onset nonallergic.

Fig 5.

Time courses for the inertance, elastance, and resistance (I_c, E_c, and R_c, respectively) of the central compartment of the series 2-compartment model of respiratory system mechanics during aerosol methacholine challenge (0 to 4.5 min) and subsequently (4.5 to 8 min). The vertical dashed line indicates the time at which methacholine aerosolization was terminated. The data are presented as means ± SE. LONA, late-onset nonallergic.

Fig 6.

Time courses for the resistance and elastance (R_p and E_p, respectively) of the peripheral compartment of the series 2-compartment model of respiratory system mechanics during aerosol methacholine challenge (0 to 4.5 min) and subsequently (4.5 to 8 min). The vertical dashed line indicates the time at which methacholine aerosolization was terminated. The data are presented as means ± SE. The slopes of R_p versus time are significantly different between the groups during challenge (ANOVA, P = 0.025). The slopes for lean asthmatics are greater than for obese controls (pairwise comparison with Bonferroni correction, P = 0.01). Postchallenge, the slopes are different among the groups (P = 0.045). The slopes of E_p versus time during challenge are significantly different between the groups (P = 0.045) but are not different postchallenge. LONA, late-onset nonallergic.

Fig 7.

Time courses for the areas A_R and A_X calculated from the fits provided by the 2-compartment model, as illustrated in Fig. 1 during aerosol methacholine challenge (0 to 4.5 min) and subsequently (4.5 to 8 min). The vertical dashed line indicates the time at which methacholine aerosolization was terminated. The data are presented as means ± SE. The slopes of A_X versus time during challenge are significantly different between groups (ANOVA, P = 0.003), with the Lean Asthma slope greater than both Obese Control (P = 0.001) and late-onset nonallergic (LONA) (P = 0.045). The slopes of A_X versus time were not different postchallenge.

Fig 8.

Tidal volume and breathing frequency versus time during aerosol methacholine challenge (0 to 4.5 min) and subsequently (4.5 to 8 min). The vertical dashed line indicates the time at which methacholine aerosolization was terminated. The data are presented as means ± SE. Breathing frequency was significantly higher in the Obese Asthma late-onset nonallergic (LONA) group compared with the other 3 groups (ANOVA, P < 0.05), which themselves were not different to each other.