Skeletal Muscle Adiposity and Lung Function Trajectory in the Severe Asthma Research Program

Abstract

Rationale: Extrapulmonary manifestations of asthma, including fatty infiltration in tissues, may reflect systemic inflammation and influence lung function and disease severity. Objectives: To determine if skeletal muscle adiposity predicts lung function trajectory in asthma. Methods: Adult SARP III (Severe Asthma Research Program III) participants with baseline computed tomography imaging and longitudinal postbronchodilator FEV₁% predicted (median follow-up 5 years [1,132 person-years]) were evaluated. The mean of left and right paraspinous muscle density (PSMD) at the 12th thoracic vertebral body was calculated (Hounsfield units [HU]). Lower PSMD reflects higher muscle adiposity. We derived PSMD reference ranges from healthy control subjects without asthma. A linear multivariable mixed-effects model was constructed to evaluate associations of baseline PSMD and lung function trajectory stratified by sex. Measurements and Main Results: Participants included 219 with asthma (67% women; mean [SD] body mass index, 32.3 [8.8] kg/m²) and 37 control subjects (51% women; mean [SD] body mass index, 26.3 [4.7] kg/m²). Participants with asthma had lower adjusted PSMD than control subjects (42.2 vs. 55.8 HU; P < 0.001). In adjusted models, PSMD predicted lung function trajectory in women with asthma (β = -0.47 Δ slope per 10-HU decrease; P = 0.03) but not men (β = 0.11 Δ slope per 10-HU decrease; P = 0.77). The highest PSMD tertile predicted a 2.9% improvement whereas the lowest tertile predicted a 1.8% decline in FEV₁% predicted among women with asthma over 5 years. Conclusions: Participants with asthma have lower PSMD, reflecting greater muscle fat infiltration. Baseline PSMD predicted lung function decline among women with asthma but not men. These data support an important role of metabolic dysfunction in lung function decline.

Keywords: longitudinal lung function; muscle adiposity; severe asthma.

Figure 1.

Strengthening the Reporting of Observational Studies in Epidemiology patient flow diagram. CT = computed tomography; PSMD = paraspinous muscle density.

Figure 2.

Example of paraspinous muscle density (PSMD) measurement on noncontrast computed tomography images. The method for measurement of the PSMD at the T12 costovertebral junction is illustrated. The right 12th rib’s junction with the T12 vertebral body is the axial location for the measurement on that scan. A 500-mm² region of interest is used. In this case, right PSMD has an average value of 42.89 HU, and left PSMD has an average value of 40.01 HU. These two measurements are then averaged to yield the mean PSMD for the participant on this specific examination. HU = Hounsfield units; Max = maximum; Min = minimum; Perim = perimeter.

Figure 3.

Comparison of mean PSMD in control subjects and participants with asthma, stratified by sex. HU = Hounsfield units; PSMD = paraspinous muscle density.

Figure 4.

Sex-stratified baseline paraspinous muscle density (PSMD) and lung function decline by tertile of PSMD. The sex-stratified model of tertiles of baseline mean PSMD predicting longitudinal FEV₁% predicted slope from mixed-effects models is illustrated. (A) Unadjusted (model 1). (B) Adjusted for asthma clinical variables (age, eosinophils, oral corticosteroid use, and exacerbations; model 4). (C) Also adjusted for BMI (model 5). This shows the trend for change in FEV₁% predicted in the SARP (Severe Asthma Research Program) III cohort over the 5-year period of observation according to baseline computed tomography PSMD. Only women showed a significant loss in lung function with lower PSMD. BMI = body mass index; HU = Hounsfield units.