Central drive and ventilatory failure in late-onset Pompe disease: At the gates of a new phenotype.

Subjects with late-onset Pompe disease (LOPD) typically present as slowly progressive proximal muscle weakness. Respiratory muscle weakness and diaphragmatic paralysis are common features, and may be the initial manifestation of the disease. There is often a poor correlation between the severity of limb and respiratory muscle weakness. Early clinical observations about disproportionate hypercapnia to the respiratory muscular weakness in late-onset Pompe disease were recognized and will be discussed with special reference to blunted respiratory drive, and the connections between early clinical observations, respiratory functional studies and anatomical findings. According to new evidence about blunted respiratory drive in Pompe disease, it is necessary to rethink what is meant by "asymptomatic Pompe disease" and propose a new phenotype with its therapeutic implications. The conceptual model of the mechanisms leading to respiratory failure in this disease could be considered according to these new findings. It may broaden the diagnostic spectrum of the adult forms and warrants a closer interaction between neurologists and pulmonologists. The recognition of this new phenotype of predominant central alveolar hypoventilation in Pompe disease will improve the understanding of the underlying mechanisms of ventilatory failure and could lead to improved future therapeutic strategies.

Pulmonary involvement of systemic lupus erythematosus: analysis of 90 necropsies.

Pleuropulmonary manifestations of systemic lupus erythematosus (SLE) have been reported to be of variable prevalence, depending on the diagnostic methods used. The objective of this study was to determine the anatomopathological prevalence and the nature of lung involvement associated with SLE and to define if there were differences in the grade and type of pulmonary involvement in patients who had died at different time periods, before or after 1996. Complete autopsy studies of 90 patients with SLE diagnosis carried out between 1958 and 2006 and their clinical records were studied. All patients fulfilled the American College of Rheumathology (ACR) diagnostic criteria for SLE. Two groups of patients were analyzed: patients who had died before 1996 and those deceased in 1996-2006. Some pleuropulmonary involvement was detected in 97.8% of the autopsies. The most frequent findings were pleuritis (77.8%), bacterial infections (57.8%), primary and secondary alveolar haemorrhages (25.6%), followed by distal airway alterations (21.1%), opportunistic infections (14.4%) and pulmonary thromboembolism (7.8%), both acute and chronic. No cases of acute or chronic lupus pneumonitis were found. Opportunistic lung infections were invasive aspergillosis, disseminated strongyloidiasis, mucormicosis and Pneumocystis carinii. Only three of 23 patients with alveolar haemorrhage showed capillaritis. The four patients with primary pulmonary hypertension (PHT) had plexiform lesions. Deceased patients' age at death (46.09 +/- 11.01 vs 30.3 +/- 11.5 years, P < 0.0001) as well as survival time from diagnosis date (11.8 +/- 11.2 vs 4.4 +/- 4.9 years, P < 0.0001) in the second time period evaluated were significantly higher. However, there were no statistically significant differences in the prevalence of any of the pulmonary manifestations. Sepsis was considered the major cause of death without significant differences in both groups. Our results show that pulmonary manifestations directly caused by systemic lupus erythematosus are very uncommon and that their prevalence has not changed in the past 10 years. Pulmonary infection is still the most frequent affection, and it is an important cause of death in patients with lupus.