A hypothesis for reactivation of pulmonary tuberculosis: How thoracic wall shape affects the epidemiology of tuberculosis

Abstract

This study was aimed at determining the cause for the high incidence of tuberculosis (TB) reactivation occurring in males with a low body mass index (BMI). Current thinking about pulmonary TB describes infection in the lung apex resulting in cavitation after reactivation. A different hypothesis is put forward for TB infection, suggesting that this occurs in subclinical apical cavities caused by increased pleural stress due to a low BMI body habitus. A finite element analysis (FEA) model of a lung was constructed including indentations for the first rib guided by paramedian sagittal CT reconstructions, and simulations were conducted with varying antero-posterior (AP) diameters to mimic chests with a different thoracic index (ratio of AP to the transverse chest diameters). A Pubmed search was conducted about gender and thoracic index, and the effects of BMI on TB. FEA modeling revealed a tenfold increase in stress levels at the lung apex in low BMI chests, and a four-fold increase with a low thoracic index, r(2) = 0.9748 P < 0.001. Low thoracic index was related to BMI, P = 0.001. The mean thoracic index was statistically significantly lower in males, P = 0.001, and increased with age in both genders. This article is the first to suggest a possible mechanism linking pulmonary TB reactivation to low BMI due to the flattened thoracic wall shape of young male adults. The low thoracic index in young males may promote TB reactivation due to tissue destruction in the lung apex from high pleural stress levels.

Diverse Cavity Types and Evidence that Mechanical Action on the Necrotic Granuloma Drives Tuberculous Cavitation

“…7,9,18,19 Finally, the role of mechanical forces in the context of pulmonary cavitation appears as a persistently unanswered question over many decades of TB literature 20e25 and recently has received renewed attention. 26,27 The mechanical model of cavitation has its origins in the preantibiotic era, and postulates that cavitation is the result of the highly dynamic environment of the lung, which is subjected to constant motion and fluctuating pressures not experienced elsewhere in the body. 28 Pioneers of this model were the research surgeons of the preantibiotic era, who used iatrogenic pneumothorax to "rest" the lung and allow closure of the cavity.…”

Impact of the Biomechanical 'Pleural Stress' Pressure Vessel Hypothesis on the Pathogenesis of Tuberculosis: Predictors of TB Reactivation and its Application to TB Screening

“…This low thoracic index (AP to lateral chest diameter ratio) or low AP diameter acts as a marker for low BMI, since AP diameter is directly related to BMI [31]. Thoracic index was statistically significantly lower in males at all age groups in a study by Takahashi and lowest in young males in their late teens and twenties [35]. Seven cohort studies on TB have linked BMI imaging such as computed tomography (CT) and combined positron emission tomography/computed tomography (PET/CT) have been used to identify minimal disease, and together with invasive sampling now play a diagnostic role in selected cases in specialist centres within high-income countries.…”

“…Low BMI is strongly associated with a low thoracic index (AP flattened chest shape) [42]. This AP flattened chest shape showed a 4-fold increase compared to round chest shape [35]. In effect this means that the apex of low thoracic index individuals is subject to a fortyfold increase in pleural stress compared to basal areas of the lung.…”

“…Can we predict those individuals that are likely to progress? Finite element computer modelling of a lung model showed that highest pleural stress was found in the apical region (10-fold increase compared to the base) and was related to an antero-posteriorly (AP) flattened chest shape (4-fold increase compared to round chest shape) [35]. This low thoracic index (AP to lateral chest diameter ratio) or low AP diameter acts as a marker for low BMI, since AP diameter is directly related to BMI [31].…”

Pathophysiological mechanism of post-lobectomy air leaks

“…The lung model created had height a of 24 cm, transverse radius b of 8 cm and anteroposterior radius c of 6 cm, see Figure 1, following methodology published by the authors (16,21). Meshing was performed using SOLID 187 element at a pressure of 40 kPa, with assumptions that the lung was elastic with a Poisson's ratio of 0.3.…”