The results of the present study reveal that fat free mass index decreases as the level of emphysema increases in both men and women with COPD. This relationship was independent of age, pack years, FEV1 (%pred), and airway wall thickness. However, muscle wasting is only moderate discriminative for the presence of emphysema. Furthermore, airway wall thickness was positively associated with fat mass index both in subjects with and without COPD.
An inverse association of %LAA to FFMI and/or FMI has previously been observed in men with an extreme smoking history [2
]. We have extended this knowledge by showing that the association applies to both genders and exists also in subjects with a far less smoking burden (e.g., mean pack years = 65 in [3
] versus 30 in the present study) and degree of emphysema (e.g., %LAA = 29% in [3
] versus 11% in the present study). Further, we observed that FFMI was independently associated with level of emphysema. This finding strengthens the hypothesis of defective regeneration processes of soft tissue in subjects with COPD and the emphysema phenotype. Although the reason for this is not yet known, various hypotheses are brought to mind. Emphysema is characterized by enlargement of the distal airspaces, caused by destruction of the airway walls [17
]. It is postulated that the inflammatory response which results in protease antiprotease imbalance, and therefore tissue destruction is extended from the lungs to whole body soft tissue. However, the link between the respiratory and the systemic inflammatory processes has to be proven yet. Another hypothesis purports emphysema as an autoimmune disease affecting the lung and other systemic elastin-rich tissues in emphysema patients [18
]. The aforementioned hypotheses are based on the assumption that loss of soft tissue is a consequence of emphysema. Indeed, patients with severe emphysema undergoing lung volume reduction surgery showed an increase in fat free mass after 6 months, implying that the systemic effects of the disease can, at least partly, be reversed [19
]. There are however no convincing data to confirm that muscle wasting is secondary to emphysema yet. In fact, it has been shown that anorexia patients have lower CT density when compared to healthy subjects [20
], pointing to the hypothesis that starvation per se
can induce secondary emphysema. In addition, although most subjects with muscle wasting had high emphysema scores, the predictive value of FFMI for emphysema is only moderate, suggesting that various pathways are involved in the pathogenesis of emphysema. More research is warranted to unravel the temporal sequence of muscle wasting, the presence of emphysema phenotype, and the interrelation between the two.
In the current study, FMI is a positive covariate of AWT-Pi10 in both subjects with and without COPD. Results of previous studies concerning the correlation between airway wall thickness and BMI are controversial; studies have shown no [2
] and positive correlations [5
]. Until now, no study related airway wall thickness with FMI. The positive association between the two seen in the present study strengthens the hypothesis of the bronchitis phenotype as CT measured airways were associated with symptoms of chronic bronchitis [15
]. However, the association is not disease-specific, questioning the usefulness of AWT-Pi10 as a specific marker to phenotype COPD.
The association between the CT phenotypes and body composition parameters did not differ between men and women. We have recently shown that there is a gender specific difference in both %LAA and AWT-Pi10 [7
]. Taken together, these findings imply that men are more susceptible to develop emphysema and thicker airway walls while the extrapulmonary manifestations of the COPD phenotypes are likely gender independent, at least for body composition.
We would like to address some limitations and strengths of the study. First, the subjects without COPD were younger than the subjects with COPD, and even tough age has been taken into account in the multivariate regression analysis, it could still influence our findings. Secondly, while COPD is considered to be a small airways disease and we calculated AWT-Pi10 using larger airways (Pi > 0.6
cm), studies have shown that CT estimates of airway wall thickness are correlated with histological measurements of small airways [21
]. Finally, obese subjects have more subcutaneous fat through which the X-rays have to penetrate resulting in less X-ray energy detected by the CT scanners and X-ray “beam hardening” effects resulting in differential effects on X-ray attenuation values. The increased amount of abdominal fat in obese subjects will also, in the supine position used during CT assessment, tend to decrease the measured lung volume. Both these factors will tend to obscure the observed relationship between %LAA and BMI. However, in the subjects without COPD, no correlation was found between %LAA and BMI, implying that the impact of this technical issue is minimal. The strengths of the present study are the large number of subjects of both genders with and without COPD, and the quantitative analysis of the CT scan.
To conclude, the present study strengthens the concept that COPD cases with muscle wasting are mainly characterized by the emphysema phenotype and decreased lung mass, although muscle wasting is not discriminative for emphysema. Airway wall thickness is positively related to fat mass index in both subjects with and without COPD. Whether airway wall thickness is a specific marker useful in phenotyping COPD has to be further investigated. These findings provide new insights into the systemic patho-physiology of COPD and its phenotypes.