**6. Cystic fibrosis**

Cystic fibrosis (CF) is an autosomal recessive monogenic disease caused by mutations in the gene coding for the CF transmembrane conductance regulator (CFTR) protein. The main clinical features of this disorder are progressive bronchiectasis and pancreatic exocrine insufficiency. Since airway inflammation and recurrent infections leading to respiratory failure represent the major causes of morbidity and mortality among CF patients, clinical research is mainly focused on these topics. The characterization of proteins from different sources and the study of their interactions within the lung microenvironment may be useful tools toward the identification of biomarkers for the diagnosis/prognosis of this disorder. The following subsections show recent reports on proteomic research in this field.

### **6.1. Induced sputum**

The proteomic approach based on 1-DE, MALDI-TOF-MS, and LC-ESI-MS/MS allowed Schulz et al. [40] to analyze high molecular mass proteins in induced sputum from (i) CF adults with and without acute exacerbation, (ii) CF children with stable disease and preserved lung function, and (iii) healthy adults and children (controls). The main high molecular mass proteins in sputum from all subjects investigated were MUC5B and MUC5AC, two mucins that, in exacerbated CF adults, seemed degraded and also showed increased sialylation and reduced sulfation/fucosylation. In addition, while two CF children showed mucin profiles similar to those of exacerbated CF adults, the remaining CF children had profiles comparable to those of healthy controls. Based on these observations, the authors suggested that the processes of mucin glycosylation and degradation may be considered as predictive biomarkers of lung condition in CF patients.

#### **6.2. Serum**

Charro et al. [41] worked on immunodepleted sera of CF patients and of healthy CF and non-CF carriers. The combination of 2D-PAGE and shotgun LC-MS/MS showed that members of the apolipoproteins family were deregulated in CF patients, while heat shock 70 kDa protein 5 and the multifunctional enzyme NDKB (an ion sensor in epithelial cells, pancreatic secretion, neutrophil-mediated inflammation, and energy production) were identified exclusively in the CF group. This interesting comparative study allowed the authors to identify deregulated proteins involved in tissue remodeling, complement system dysfunction with consequent impairment on defense mechanisms and chronic inflammation, nutritional imbalance, and colonization by *P. aeruginosa*.
