Pulmonary & Respiratory Medicine

Pulmonary alveolar microlithiasis (PAM) is a rare disease of unknown origin in which calcific concretions collect in alveolar spaces. No known cause for the disease had been identified and there appears to be no systemic disorder of calcium metabolism. Plain chest X-ray shows a white lung consisting of fine sandlike micro calcification diffusely scattered throughout both lungs with high density at lung basis. CT reveals ground glass haze with inter and intra lobular septal thickening suggestive of crazy paving pattern. We here report the typical X-ray and HRCT images of a case of PAM: a rare disease characterized by wide spread sand like intra alveolar calcifications.

Aim: The aim of this study was to develop a lung-targeted, mouse model of cigarette smoke-induced inflammation that can be used to study the pathophysiological changes that occur in the lungs of human smokers and patients with chronic obstructive pulmonary disease (COPD).

Materials & methods: Cigarette smoke extract (CSE) was prepared freshly daily. Intranasal administration into female mice was performed once daily for up to 3 weeks.

Results: CSE significantly increased airway macrophages after 3 and 4 days of dosing, and then declined over the subsequent 2 weeks. However, airway neutrophils were elevated after a single dose of CSE, and at all subsequent time points. Muc5AC was significantly increased in the Bronchoalveolar lavage (BAL) of CSE-treated animals compared to control mice (P<0.05), but TNF-α concentrations decreased in a dose-dependent manner. In animals challenged with CSE for 4 consecutive days, a PDE4 inhibitor (Roflumilast; 10 mg/kg BID) significantly inhibited both macrophages (P<0.01) and neutrophils (P<0.001), a steroid (prednisolone; 10 mg/kg BID) had no effect on either macrophages or neutrophils and an oral p38 inhibitor (PHA-818637; 10 mg/kg BID) inhibited macrophages (P<0.05), but not neutrophils. CSE inhibited lipopolysaccharide-induced airway neutrophilia.

Conclusion: This model reflects many aspects of human COPD including pulmonary leucocytes, mucin, TNF-α and response to clinical therapeutic agents and may be useful in assessing the efficacy of potential therapies