**6. Viral infection in patients with cystic fibrosis**

Progression of CF respiratory disease is influenced by viral infection. Respiratory viral infections include respiratory syncytial virus (RSV), rhinovirus,

*Cystic Fibrosis - Heterogeneity and Personalized Treatment*

most common [25, 26].

**3.3 Nontuberculous mycobacteria species in patient with cystic fibrosis**

**4. Airway colonization process in patients with cystic fibrosis**

by *P. aeruginosa* infection in the latter stages of CF.

tance to various antibiotics is increased [27, 34].

Colonization of microorganisms in respiratory tract infection within young CF patient includes common pathogens such as *S. aureus* or *H. influenza* then succeeded

It is well established that *Pseudomonas aeruginosa* is a frequent and virulent pulmonary pathogen in patients with CF [27]. After a period of intermittent colonization, the organism becomes permanently established and is difficult to eradicate. Most patients with CF become chronically infected with wild-type *P. aeruginosa* strains in early childhood [28]; prevalence increases with age, so that as many as 80% of patients with CF are infected by the time they reach 20 years [27]. During the years following initial colonization, the wild-type strains uniformly mutate into mucoid variants [28]. Conversion to the mucoid phenotype is thought to be driven by the unique CF microenvironment [29–31]. For patients with CF, this conversion results in a significant increase in morbidity and mortality accompanied by a measurable decline in pulmonary function [28]. The mucoid matrix is believed to allow the formation of protected biofilm microcolonies [30, 32] and provide increased resistance to opsonization, phagocytosis, and digestion [33]. Furthermore, resis-

The potentiality of pathogenic bacterial colony morphotypes in *P. aeruginosa* evolved to a non-swimming phenotype form. So, motility is considered as one of the first steps of *P. aeruginosa* in CF lungs that lead to adaptation steps including biofilm formation and progress to chronic infection. Also, impaired swimming motility seemed to be a candidate to disease marker of *P. aeruginosa* infection development. So far, the pathological changes in the lungs are best studied due to the high mortality rates linked to poorer lung function and recurrent development

Also, the lungs of people with cystic fibrosis are predominantly colonized with *Pseudomonas aeruginosa* using the following mechanism: firstly, reduced mucociliary clearance combined with the malfunction of antibacterial peptides; secondly, impaired defense of the lungs due to low levels of glutathione and nitrous oxide; thirdly, reduced ingestion of bacteria by lung cells; and finally, increased numbers

On the other hand, earlier age of infection with *P. aeruginosa* in our population was strongly associated with greater likelihood of severe lung disease later in life, most particularly in those subjects who acquired *P. aeruginosa* before the age 5; the

NTM are wide environmental microorganisms causing chronic pulmonary infection in lung diseases such as CF. Also, pulmonary disease caused by NTM has a major threat with CF and difficult to diagnose and problematic to treat according to the US Cystic Fibrosis Foundation (CFF) and European Cystic Fibrosis Society (ECFS). Additionally, the most common NTM species identified in CF are the slow-growing *Mycobacterium avium* complex (MAC) including *M. intracellulare*, *M. avium*, and *M. chimaera* and the rapid-growing *M. abscessus* complex (MABSC) including subspecies of *M. a. abscessus*, *M. a. massiliense*, and *M. a. bolletii*. Other less common NTM species include *M. kansasii*, *M. simiae*, and *M. fortuitum* [24]. In addition, there are more than 100 types of NTM, and more are being found every year. The reported prevalence of NTM in CF varies widely from 45 to 40% with *Mycobacterium avium* complex and *Mycobacterium abscessus* complex being the

**26**

of infections [18].

of bacterial receptors [35].

influenza, para influenza, and adenovirus which is RSV and influenza infection leading to decreases in lung function [41]. Also, viral respiratory infections show pronounced and long-lasting effects on patients with CF, resulting in significant declines in forced vital capacity (FVC), forced expiratory volume in 1 second (FEV-1), and significant increases of both the frequency and duration of hospitalizations especially that the frequency of viral respiratory infections is closely associated with pulmonary deterioration in patients with CF [42]. Additionally, viral respiratory infections occur in equal frequency in CF patients and healthy controls which in CF patients viral upper respiratory tract infections are associated with lower respiratory tract symptoms in 31–76%. Viral infections cause long-term respiratory morbidity in CF patients [43].
