**4. Results**

One hundred and fifty-one CF patients have been hospitalized between 2010 and 2020, due to PEX. Positive respiratory specimen cultures for NTM were obtained in 11 patients (7%). The group consisted of nine females and two males, mean age—35.7 years (SD 9.96 years). Non-tuberculous mycobacterial lung disease (NTMLD) was diagnosed in eight patients, and respiratory system colonization with NTM—in three. Anti-mycobacterial therapy was administered in six patients with NTMLD, one patient refused treatment; in one case the treatment was delayed due to large clinical improvement in the course of PEX therapy. The patients were treated according to European Society for Cystic Fibrosis recommendations [6].

#### *4.1. Clinical Data*

Mean BMI was—20.2 kg/m<sup>2</sup> (SD 2.78 kg/m2). Mean spirometry values were: FVC— 73.8% (SD 16.7%) predicted, FEV1—58.6% (SD 20.6%) predicted, FEV1/FVC—70.1 (SD 14.33).

Allergic bronchopulmonary aspergillosis (ABPA) was diagnosed in five patients (46%), three of them had been treated with prednisone at the time of NTM isolation. All of the patients were non-smokers.

Type 1 diabetes mellitus was diagnosed in three patients (27%), gastroesophageal reflux—in one, and hypothyreosis—in one.

On admission, increased expectoration of purulent sputum was present in 11 patients (100%), decrease in exercise tolerance—in eight patients (73%), loss of appetite—in eight patients (73%), and increased body temperature—in six (55%), hemoptysis—in three (27%).

#### *4.2. Microbiological Analysis*

## 4.2.1. NTM

AFB smears were positive in four (36%) patients. In all of them, Gene Xpert MTB tests were negative. Cultures and phenotyping revealed the presence of: *M. avium*—in six patients, *M. chimaera*—in two, *M. kansasii*—in one, *M. abscessus*—in one, *M. lentiflavum*—in one (Table 1).


**Table 1.** Results of microbiological evaluation in 11 CF patients with positive NTM isolates.

NTM—nontuberculous mycobacteria; Case N◦—case number; NTM sputum N◦ pos.—number of positive NTM sputum specimens; NTM b.wash. No pos.—number of positive NTM bronchial washing specimens; *Psed. aerug.*—*Pseudomonas aeruginosa*; *Staph. aureus*—*Staphylococcus aureus*; *Asp. fumig.*—*Aspergillus fumigatus*; *Cand. albic.*—*Candida albicans*; *Achr. xylosox.*—*Achromobacter xylosoxidans*; *M. kansasii—Mycobacterium kansasi*; *M. avium*—*Mycobacterium avium; M. lentiflav.—Mycobacterium lentiflavum; M. chimaera*—*Mycobacterium chimaera*; *S. maltoph.*—*Stenotrophomonas maltophilia*; *P. fluoresc.*—*Pseudomonas fluorescens*; *E. coli*—*Escherichia coli; Kl. pneum.*— *Klebsiella pneumoniae*; *E. cloacae*—*Enterobacter cloacae*; *Penicil.* spp.—*Penicillium species*; *C. glabr.*—*Candida glabrata*; *A. flavus*—*Aspergillus flavus*.

All of the patients fulfilled the microbiological criteria of NTMLD diagnosis (at least two positive sputum samples or one positive bronchial washing sample).

#### 4.2.2. Other Pathogens

At the time of NTM isolation seven patients (63%) were colonized with *Pseudomonas aeruginosa (P. aeruginosa)*, six (55%)—with *Staphylococcus aureus (S. aureus)*, and four patients (36%)—both *P. aeruginosa* and *S. aureus* (Table 1).

Respiratory cultures were positive for fungi—in 10 (91%) patients, *Aspergillus fumigatus* (*A. fumigatus*) was isolated in 5 (45%), *Candida albicans* (*C. albicans*)—in 9 (82%), and both types of fungi—in 5 (45%) patients (Table 1).

#### *4.3. Radiological Data*

Chest CT revealed bilateral bronchiectasis, localized predominantly in the upper lung lobes and thickened bronchial walls with the signs of mucus plugging in the bronchial lumen, in all patients. In three patients—enlarged mediastinal lymph nodes, and in two— air trapping was described. Partial lung cirrhosis was noted in one patient.

In five out of 11 patients, chest CT was indicative of NTMLD. New nodular infiltrations with cavitation were described in three patients and new areas of centrilobular nodules in the middle lobe and lingua—in two patients (Figures 1 and 2). In the remaining six patients, the radiologic appearance of chest CT was not suggestive of NTMLD.

**Figure 1.** *Cont.*

**Figure 1.** 26-years old female with cystic fibrosis and NTMLD (cavitary form). Evolution of chest CT changes from 2018 (**<sup>a</sup>**–**<sup>c</sup>**) to 2020 (**d**–**f**). (**<sup>a</sup>**–**<sup>c</sup>**) Chest CT scans (lung window, axial and coronal view) demonstrating bronchiectasis of the large and smaller airways (black arrows), centrilobular nodules (white arrows) and bronchial wall thickening predominating in the upper lobes. (**d**–**f**) Chest CT images (lung window, axial and coronal view) demonstrate progression of changes—bronchiectasis has worsened, inflammatory changes became larger, thick wall cavities have appeared (black arrows) which can indicate pulmonary infection caused by NTM.

**Figure 2.** Forty two-year old female with cystic fibrosis and NTMLD (cavitary form). (**a**) CT scan (lung window, axial view) shows thick walled cavity in the 6th segmen<sup>t</sup> of right lung (black arrow) which may sugges<sup>t</sup> pulmonary NTM infection. (**b**) CT scan (lung window, axial view) after 6 years in the place of previously visible cavity shows consolidation (black arrow). (**c**) CT scan (lung window, coronal image) presents upper right lobe collapse with cystic bronchiectasis involving the whole bronchial tree (black arrow).
