Elena Paracchini

Pulmonary alveolar proteinosis: diagnostic and therapeutic challenges

Pulmonary Alveolar Proteinosis (PAP) is a rare syndrome characterized by pulmonary surfactant accumulation within the alveolar spaces. It occurs with a reported prevalence of 0.1 per 100,000 individuals and in distinct clinical forms: autoimmune (previously referred to as the idiopathic form, represents the vast majority of PAP cases, and is associated with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) auto-antibodies; GMAbs), secondary (is a consequence of underlying disorders), congenital (caused by mutations in the genes encoding for the GM-CSF receptor), and PAP-like syndromes (disorders associated with surfactant gene mutations). The clinical course of PAP is variable, ranging from spontaneous remission to respiratory failure. Whole lung lavage (WLL) is the current standard treatment for PAP patients and although it is effective in the majority of cases, disease persistence is not an unusual outcome, even if disease is well controlled by WLL.In this paper we review the therapeutic strategies which have been proposed for the treatment of PAP patients and the progress which has been made in the understanding of the disease pathogenesis.

C reactive protein and alpha1-antitrypsin: relationship between levels and gene variants

The first step in laboratory diagnosis of alpha1-antitrypsin deficiency (AATD) is the determination of alpha1-antitrypsin (AAT) serum levels; these levels in turn are influenced by the inflammatory status. C reactive protein (CRP) has been proposed as a marker of systemic inflammation. Single nucleotide polymorphisms (SNPs) in the CRP gene have been associated with differences in baseline CRP levels. The purpose of this study was to investigate the relationship between CRP and AAT in the AATD diagnostic setting and to verify whether variations in the CRP gene could influence CRP. We determined AAT and CRP levels in 362 consecutive dried blood spot (DBS) samples submitted for AATD diagnosis and genotyped 3 CRP gene SNPs (rs1205, rs3093077, and rs3091244) associated with variations in serum CRP concentrations. To this aim, we developed a method to measure CRP in a DBS with a good correlation with CRP measurement in serum (r2=0.9927). We showed then that systemic inflammatory status parallels increased levels of AAT (80% of subjects with intermediate AATD and a CRP>0.8 mg/dL had an AAT level above the cut-off of 113 mg/dL) and that this increase might mask the presence of AATD variants. No association was detected between CRP levels and the 3 CRP gene polymorphisms. Simultaneous determination of CRP and AAT is useful in the correct diagnosis of heterozygotes carrying intermediate AATD genotypes; their genetic influence on the CRP level is negligible.

Proteinosi alveolare polmonare: caratteristiche cliniche della casistica raccolta da un centro nazionale di riferimento

Pulmonary alveolar proteinosis is a disorder characterized by the accumulation of lipoproteinaceous, eosinophilic, PAS-positive material within the alveolar spaces. PAP is an extremely rare disorder; it occurs in three distinct clinical forms: autoimmune, secondary and congenital. The clinical course of PAP is variable, ranging from spontaneous remission to serious respiratory insufficiency. Whole lung lavage (WLL) is the gold standard treatment. The post-WLL outcomes may range from complete recovery to persistent disease, however well controlled by the WLL which eventually follow. The aim of this work was to analyze data regarding the 81 patients who turn to our Centre, which is considered the national reference Institute, by evaluating the clinical, laboratory, functional and radiological aspects. In this way our work provides a global vision of this rare respiratory disorder.

L’epidemiologia dell’asma bronchiale

L’asma e una delle patologie piu diffuse al mondo, si stima che ne siano affetti circa 300 milioni di persone. La sua prevalenza varia notevolmente da nazione a nazione e all’interno della stessa nazione, in conseguenza a varianti genetiche con una sovrapposizione di fattori socio-economici e ambientali. La prevalenza di asma nel mondo e aumentata dalla meta del secolo scorso fino agli anni ‘90, ma da quel momento non e chiara la sua evoluzione temporale. La prevalenza di asma nella popolazione infantile sta aumentando nei paesi in cui era minore mentre nei paesi occidentali nei quali era gia elevata, e stabile o in diminuzione. Il cambiamento del trend della prevalenza negli adulti e ancora controverso. In parecchie aree italiane tra il 1991 e il 2010 sono state condotte ripetute indagini cross-sectional con un identico disegno dello studio ed identici metodi di valutazione. In Italia si sta verificando ancora un incremento della prevalenza dell’asma bronchiale che sembra inserirsi nell’ambito dei cambiamenti generali all’interno delle varie nazioni che portano ad un livellamento delle differenze nei tassi di prevalenza. Appare necessario quindi focalizzare l’attenzione sulla prevenzione e sul trattamento precoce ed adeguato di tutti i casi di asma.