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As calcification also requires stabilization of the lesion, this is related to a lower encapsulation SB203580 molecular weight capacity, which may be due to the lesser ability of the interlobular septae to react against minimal lesions as a result of the enormous stress to which it is subjected (Suki et al., 2013) as the lung must support its own weight. Similar to a suspended coil spring, the largest alveoli and the greatest stress in the lung are found in the apex, and this may weaken the elastic fibers (Gurney and Schroeder, 1988). Interestingly, a high pH has also been reported to favor the induction of foamy macrophages, as weak bases tend to concentrate intracellularly at higher extracellular pH (Gurney and Schroeder, 1988). It has been extensively demonstrated that foamy macrophages are responsible for the drainage of M. tuberculosis out of the lesions, thus playing an important role in bronchogenic dissemination (Cardona, 2009), and they have also been linked to the attraction of neutrophils at the onset of exudative lesions induced in C3HeB/FeJ mice (Marzo et al., 2014). A definitive proof of the favorable conditions for TB progression in the upper lobes is the observation that the nodules are initially disseminated diffusely throughout the lung in miliary TB, whereas in advanced disease, the foci are larger in the upper lobes (2�C3 mm) than in the lower (1 mm) (Auerbach, 1944; Felson, 1952; Gurney and Schroeder, 1988) (Table ?(Table11). However, this is not specific to TB as the upper lobes are also involved in a large number of lung diseases (Ryu and Swensen, 2003; Nemec et al., 2013), including cavitated lesions with different infectious origins (Klebsiella, Pneumocystis, etc.) (Gadkowski and Stout, 2008), primary cancer (Byers et al., 1984), and metastasis (Yanar et al., 2014), or even the presence of chronic obstructive pulmonary disease (COPD) due to the induction of emphysema (Suki et al., 2013). Primary or post-primary lesions? With the systematic use of chest X-rays to diagnose TB from the end of the Second World War (>1945) (Bynum, 2012), the concept whereby initial infection occurs in childhood but, if controlled, is then detected in adulthood in the form of a calcified nodule in the parenchyma and in the draining hilar lymph node (Ghon Complex) soon appeared (Canetti, 1950). However, adults with TB symptoms tend to develop an infiltration in the upper lobe, with no involvement of the draining lymph node (Adler, 1953; Poppius and Thomander, 1957). These findings led to the leading concept (known as the ��unitary concept��) that post-primary disease is a consequence of reactivation of an old lesion generated during the primary infection in childhood, which subsequently leads to the haematogenous dissemination of different lesions until an immune response is generated.