The pulmonary phenotype was the most frequent finding, affecting 71 patients (92.2%). Of the 77 cases, 50 (64.9%) performed spirometry maneuvers, with the following results: 25 (50.0%) presented normal spirometry, 15 (30.0%) mild obstructive ventilatory disorder (OVD), 5 (10.0%) moderate OVD, 3 (6.0%) severe OVD and 2 (4.0%) with mixed disturbances. The average forced expiratory volume in one second (FEV1) was 83% (±19) and the forced vital capacity (FVC) was 92% (±18) (Table 2).

Chronic colonization was evident in 57 (74.0%) of the cases evaluated, with the following most frequent pathogens: Staphylococcus aureus 43 cases (55.8%) and Pseudomonas aeruginosa 27 cases (35.1%).

Only three patients (3.9%) presented with the pulmonary phenotype, without extrapulmonary manifestations.

Pancreatic involvement occurred in 67 cases (87.0%), the second most frequent phenotype. Most of the patients presented pancreatic insufficiency. About 14% presented CFRD and only one (1.3%) patient had pancreatitis (Table 2).

Gastrointestinal involvement was observed in 36 cases (46.8%), with constipation being the most common manifestation (33.8%). Table 2 describes the frequency of other gastrointestinal manifestations observed.

Hepatobiliary involvement occurred in 48 (62.3%) cases, with hepatomegaly in 22.1% of the total sample. The other hepatobiliary manifestations are described in Table 2. Among the patients with hepatobiliary involvement, 26 (54.2%) were treated with ursodeoxycholic acid (UDCA), and 19 (73.1%) of these presented reduced liver enzymes and improved echoradiographic aspects.

Of the 77 cases, 42 (54.5%) were subjected to hepatic elastography. Fibrosis (>5.0 kPa) was detected at 14 (33.3%), with a median of 6.85 kPa (2.5–14.4 kPa). The highest degree of fibrosis (14.4 kPa) was observed in a 14-year-old patient. The altered FibroScan® presented a statistically significant correlation with increased liver enzymes (p=0.018) and portal hypertension (p=0.018) (Table 3).

The diagnosis was made earlier in the group with pancreatic insufficiency, with a median of 5.0 months (1–144 months) when compared with the group with pancreatic sufficiency, with a median of 84.0 months (3–168 months) (p=0.01), as described in Table 4.

The median age of diagnosis prior to neonatal screening was 6.0 months (1–168 months), and subsequent to implementation of the test was 3.0 months (1–14 months) (p=0.02) (Table 4).

The pulmonary phenotype was the most frequent (92.2%), similar to that described by Rizzo et al. (92.0%) [17]. Half of the patients capable of performing spirometric maneuvers showed normal spirometry, higher than the reported data in the REBRAFC, where 40% of the patients underwent normal spirometry [14]. The averages of FEV1 and FVC were also better than those described in the REBRAFC [14]. It has been reported that BMI values above the 50 percentile are associated with better pulmonary function [18], which explain the favorable pulmonary indices in this study.

The colonization of S. aureus in more than half of the patients in this study is consistent with the literature. According to Goss and Muhlebach [19], S. aureus is one of the earliest and most frequent pathogens isolated from the respiratory tract of patients with CF. The case study involving P. aeruginosa showed a lower frequency than that of REBRAFC [14].

The importance of recognizing the non-respiratory complications of CF is well known [20]. Only 3.9% of the evaluated patients presented no extrapulmonary manifestations involving pancreatic, gastrointestinal and hepatobiliary dysfunction.

The pancreatic phenotype was the second most frequent, with pancreatic insufficiency diagnosed in most of the cases (Table 2). It is known that 90% of CF carriers are pancreatically insufficient, with malabsorptive syndrome being the classical clinical presentation, also with steatorrhoea and growth insufficiency, mainly due to poor absorption of nutrients [21].

The prevalence of CFRD observed resembles the known condition in Brazil (13.3%) [18]. However, it is higher than that reported by international registration (2.9%) [16], probably justified by ethnic and/or geographical differences.

Only one patient, who had pancreatic insufficiency, showed signs of chronic pancreatitis in an abdominal ultrasound. It is known that the imaging of patients with CF reveals fatty substitution, calcification and atrophy of the pancreas consistent with chronic lesion [1], which may justify the findings in the described patient.

Gastrointestinal involvement was present in almost half of the cases, reflecting the trend reported in the Brazilian literature [17]. Constipation was the most frequent gastrointestinal manifestation (33.8%), similar to that described by Gelfond and Borowitz (32.0%) [2]. It resulted in increased viscosity of intestinal content as well as distal intestinal obstruction syndrome (DIOS) [2]. In this study, 11.7% of the patients presented DIOS, with incidence similar to that observed in world centers [22]. This is a unique condition of CF and is characterized by complete or incomplete fecal obstruction in the ileocecal region [2].

The prevalence of identified GERD (9.1%) was higher than in REBRAFC (5.6%) [14], but lower than that reported by foreign studies [23]. The prevalence variation is justified by the difference in the methods used to define GERD.

It is known that the occurrence of GERD in these patients is 6 to 8 times greater than in healthy children. Several factors contribute to the increase: prolonged gastric emptying, medicines, and increased abdominal pressure by coughing and respiratory physiotherapy [24].

The prevalence of meconium ileus (9.1%) was close to that described in literature [25]. This condition is considered a neonatal emergency, often associated with serious mutations [25].

The occurrence of rectal prolapse was observed in 2.6% of the cases (Table 2). The literature estimates that less than 5% of CF patients will have rectal prolapse [26]. Rectal prolapse is probably attributed to the earlier diagnosis of the disease by screening newborns, prevention of constipation and better formulations of pancreatic enzyme replacement therapy [4]. Although CF is not the cause of rectal prolapse in most cases, it should be included in the differential diagnosis [4].

The prevalence of peptic ulcerative disease (PUD) was 2.6%, and negative for Helicobacter pylori in all cases. It has already been described that despite the reduction of bicarbonate secretion in patients with CF, habitual prevalence or even decreased PUD and infections by H. pylori are observed [27]. This “CF paradox” may be due to the bicarbonate retained in the cytoplasm of the enterocyte, which prevents injury and ulcer formation, or due to frequent use of antibiotics [27].

Only one (1) patient presented fibrosing colonopathy, reinforcing reduced incidence of this condition after standardization of the pancreatic enzyme replacement therapy described in the literature [4].

The frequency of hepatic involvement observed in this study (62.3%) was greater than that described by Salvatore et al. (5.7% in children) [28]. In a Brazilian study, hepatobiliary disease was diagnosed in 16.4% of the patients, and it occurred as an initial manifestation of CF in 55.6% of these cases [29]. This variation in prevalence may be justified by the difference in the methods used for the diagnosis of liver disease associated with CF. In this study, it was not possible to perform the genetic study, therefore, it is not possible to evaluate if the observed prevalence was related to the genotype.

It is known that most CF patients will at some point present evidence of liver changes [30]. Currently, liver disease in CF is considered the third leading cause of death [31].

The prevalence of observed hepatomegaly (22.1%) is close to that reported in the literature (6–30%) [31]. However, the observed rate of neonatal cholestasis (11.7%) was different from the literature, where less than 2% of children with CF suffered from this condition [32]. An increase in liver enzymes (10.4%) within patients was observed. According to Flass and Narkewicz [33], the transient elevation of transaminases is often observed, often from idiopathic cause or due to antibiotics used to treat exacerbations, which undergo hepatic metabolism [33]. The occurrence of hepatic steatosis in this series (7.8%) differs from the prevalence of 23% to 67% reported in another study [30]. It is the most common liver lesion in patients with CF [33], and appears unrelated to the defect in the CFTR gene, but may be indirectly related to malnutrition, deficiency of essential fatty acids and oxidative stress, often occurring in these patients [31]. These factors may explain the low prevalence of hepatic steatosis, since most of the patients studied were eutrophic.

The prevalence of cholelithiasis in this study (6.5%) is reflective of the prevalence of 1% to 10% described in a revision study [31]. Of all the cases evaluated, 7.8% presented splenomegaly, 6.5% portal hypertension, 3.9% esophageal varicose veins, and 1.3% cirrhosis. It is questionable whether cirrhosis in CF is necessary for the development of portal hypertension, because according to Witters et al. [34], noncirrhotic portal hypertension (PH) can occur secondary to a vascular component. However, additional studies are needed to better elucidate this subject.

More than half of patients with hepatobiliary involvement were treated with UDCA, with a reduction in liver enzymes and improved echographic aspects in most cases. UDCA shows choleretic activity, reducing bile destruction, preventing bacterial translocation, and the development of endotoxin [30]. Thus, UDCA treatment has a beneficial effect on the activity of liver enzymes, in biliary drainage, hepatic histology, as well as in altering the profile of essential fatty acids [30].

Several research studies have been undertaken in the last decade to identify a non-invasive method for evaluating hepatic fibrosis, such as hepatic transient elastography (TE) [13]. In this study, fibrosis was observed in approximately 1/3 of the patients submitted for examination. The median (6.85 kPa) resembles the one (5.6 kPa) described by Witters et al. [35]. According to the literature, liver disease usually occurs after 10 years of disease evolution, and the fibrosis index is associated with the age of patients [13]. Similar to this study, measurements of hepatic rigidity in TE were significantly higher in the group manifesting clinical hepatic disease, altered liver biochemistry, as well as in the group with splenomegaly detected by ultrasound [35]. Thus, liver rigidity represents a viable non-invasive marker to detect CF, and to exclude PH.

This study found that the diagnosis of CF was earlier in the group with pancreatic insufficiency, when compared with the group diagnosed with pancreatic sufficiency (Table 4), possibly due to the manifestation of symptoms related to malabsorption syndrome of pancreatic insufficiency.

A reduction in the median age of diagnosis was observed after the implementation of the neonatal screening, similar to that described in REBRAFC 2014 [14] (Table 4). Although this study made descriptive analysis, the findings demonstrate the importance of extending the scope of neonatal screening for CF, with active investigation, in order to ensure early diagnosis and treatment to prevent damage.

In conclusion, the pulmonary phenotype was the most common, while the extrapulmonary manifestations were frequent and clinically relevant, and warrant early detection in the course of the disease followed by prompt treatment. Most patients, despite manifesting pancreatic insufficiency, revealed satisfactory nutritional status, demonstrating the effectiveness of treatment. The diagnosis was made earlier in patients with pancreatic insufficiency. The median age of diagnosis was reduced after the implementation of neonatal screening test by the public health service of the Federal District of Brazil, underscoring the significance of universal adoption of this test internationally.