Methods
A retrospective study in a CF referral center was performed. Demographic, clinical, and laboratory data were obtained from 104 patients with CF seen in the last decade of the 20th century, from 1990 (time zero) to 2000 (DI); all data were collected from the patients' medical records in the year 2000. The same data were obtained from 181 patients with CF treated in the first decade of the present century, from 2001 (time zero) to 2010 (DII); all data were collected from the patients' medical records in the year 2011. The number of patients with CF enrolled in both decades equaled the total number of patients with CF followed at the referral center in the stipulated timeframe. The diagnosis of CF was confirmed by two sweat tests with chloride concentrations of >60 mEq/L (gold standard diagnostic tool) and/or identification of two CFTR mutations. Patients with CF who had undergone lung transplantation were not enrolled.
Demographic, Clinical, and Laboratory Markers
The demographic, clinical, and laboratory variables analyzed in this study were sex (male/female), ethnicity (Caucasian or non-Caucasian), age, age range, number of deaths, clinical manifestations (respiratory and digestive), age at diagnosis, comorbidities [pancreatic insufficiency (PI), meconium ileus (MI), and diabetes mellitus (DM)], nutritional status as determined by weight and height on a growth curve (weight and height below the 10th percentile), oxygen saturation (SpO2) (>95%, 91%–95%, or <91%), sweat chloride level, microorganisms in the sputum (Staphylococcus aureus, mucoid and nonmucoid Pseudomonas aeruginosa, and Burkholderia cepacia), spirometry findings (normal, restrictive lung disease, obstructive lung disease, or mixed respiratory disorder), genetic screening for the CFTR mutations [F508del (rs113993960, c.1521_1523delCTT), G542X (rs113993959, c.1624G > T), N1303K (rs80034486, c.3909C > G), G551D, R553X (rs74597325, c.1657C > T), and W1282X (rs77010898, c.3846G > A)], Shwachman-Kulczycki score (SKS) (excellent or good, mild, or moderate or severe), and fecal fat.
Spirometry
Spirometric testing was performed according to the following American Thoracic Society standards:
Obstructive lung disease: less than the 5th percentile of the ratio of the predicted forced expiratory volume in the first second to the forced vital capacity (FEV1/FVC). Reduction of flow in a patient with low lung volume is not specific to small airway disease. Concomitant decreases in FEV1 and FVC are commonly caused by poor effort, but can rarely reflect airflow obstruction. Confirmation of airway obstruction requires lung volume measurement.
Restrictive ventilatory disturbance: total lung capacity below the 5th percentile of the predicted value. Reduced FVC does not prove the presence of a restrictive lung defect, but is suggestive of pulmonary restriction when the FEV1/FVC is normal or increased.
Mixed respiratory disorder: FEV1/FVC and lung capacity below the 5th percentile of the predicted value.
Spirometric testing was performed in patients >7 years of age using a CPFS/D spirometer (Medical Graphics Co., Saint Paul, MN, USA). The data were recorded by PF BREEZE software vs 3.8B for Windows 95/98/NT (Medical Graphics Co.).
SKS Analysis
The SKS was determined by two previously trained professionals, and in case of disagreement, a third evaluator was considered.
Sputum Collection
The patients' sputum was collected by spontaneous sputum sampling, induction by physiotherapy maneuvers, or collection of oropharyngeal swabs for analysis of the microorganism colonizing or infecting the airways. Examinations were performed in the Pathology Laboratory at the Clinical Hospital of the State University of Campinas.
IRT was implemented in our center in 2010. Therefore, the comparative analysis of the two decades did not include patients with CF who underwent neonatal screening.
Statistical Analysis
The Statistical Package for the Social Sciences v.21.0 (SPSS, Inc., Chicago, IL, USA) was used for statistical analysis. For descriptive analysis, we used mean, median, and standard deviation for continuous variables and absolute frequency (percentage) for categorical variables. Fisher's exact test and the χ test were performed to compare the groups using categorical variables. In cases of differences in the data between the periods analyzed, the odds ratio (OR) and 95% confidence interval (95% CI) were calculated. The alpha value was 0.05. The Ethics Committee in Research of the State University of Campinas (#508/2008) approved this study.